镉对DNA代谢的影响和大豆异黄酮的保护作用
|
摘要
镉(Cadmium，Cd)是一种在土壤沉积物、空气和水中广泛存在的重金属元素，1940年起镉就被大规模的应用。镉的主要职业接触有镉的熔炼、生产和回收。非职业接触中饮食是主要的来源，还有吸烟。
镉被美国环境保护署(EPA)列为126个优先考虑的污染物之一，能造成骨质疏松、肾损伤、贫血等。镉是一种致癌物，职业镉接触同肺癌、前列腺癌、胰腺癌和肾癌相关。镉作为肺的致癌物，镉被国际癌症研究机构(IARC)和美国国家毒理学机构(NTP)定义为1类致癌物。
尽管全世界对镉的细胞毒性和致癌性进行了大量的研究，对于其分子机制研究也越来越重视，但是具体的机制并不清楚。有实验研究发现，镉能直接和间接造成基因毒性，例如引起DNA链的断裂、DNA-蛋白交联、氧化DNA损伤和染色体畸形等，这些可能是镉细胞毒性和致癌的重要机制。镉能激活或失活很多细胞因子。有报道肿瘤抑制基因(p53)和原癌基因(c-jun、c-fos和c-myc等)能够被镉激活。作为一个重要的抑癌基因，p53同时也能使哺乳动物细胞DNA损伤后被诱导凋亡，或引起细胞周期阻滞并进行DNA修复等。本课题主要以细胞模型为研究对象；使用两种方法使野生型p53失活，进而研究镉引起野生型p53细胞和p53功能缺陷型细胞的DNA损伤、细胞周期的检查点反应、DNA合成、微卫星突变率、原癌基因表达等的影响。彗星实验表明镉能造成野生p53细胞和p53功能缺陷型细胞的DNA损伤，进一步引起不依赖于p53的速发型G2检查点反应和依赖于p53的迟发型G2检查点反应，还观察到镉能抑制细胞DNA合成。镉对不同细胞周期的细胞进行染毒发现，S期的细胞比G1期的细胞更为敏感，提示S期可能是镉作用于细胞的靶作用期。Gadd45是G2细胞向M期细胞的过渡中发挥调控作用重要的蛋白，镉诱导Gadd45的表达可能是镉引起的速发型G2检查点反应的调控机制，Gadd45的诱导不依赖于p53、ATM。镉诱导的迟发型G2检查点反应依赖于p53但不依赖于ATM。
大豆异黄酮是一种植物雌激素，它的结构同17-β雌二醇相似，但是雌激素样活性很低。流行病学、动物实验和细胞研究发现大豆异黄酮能预防癌症的发生，并能抑制癌细胞的生长和增殖。
通过实验研究发现，大豆异黄酮能保护镉造成的DNA损伤，大豆异黄酮可能通过其抗氧化自由基的作用中和镉产生的氧化自由基而拮抗镉造成的DNA损伤作用。这可能是植物雌激素预防癌症发生一个重要的机制。
研究还发现，大豆异黄酮能抑制癌症细胞的增殖和生长，其抑制癌症细胞的增殖和生长的作用机制和其预防癌症的发生的作用机制不同，细胞周期和相关基因表达研究表明，大豆异黄酮抑制癌症细胞的增殖和生长中，PTEN基因具有重要的作用。
镉能造成细胞的DNA损伤，进一步引起不依赖于p53速发型G2检查点反应和依赖于p53的迟发型G2检查点反应，使部分细胞的细胞周期永久阻滞，进而细胞老化死亡。而没有发生细胞周期阻滞的DNA受损细胞，带着受损的DNA进入子代细胞，这可能是镉诱导癌症发生的一个重要机制，植物雌激素能保护镉造成DNA损伤。
Cadmium, a heavy metal, is a member of group IIb in the periodic table of elements which is present in soils, sediments, air and water. Major occupational exposure occurs in non-ferrous metal smelters, in the production and processing of cadmium, its alloys and compounds and, increasingly, in the recycling of electronic waste. Non-occupational exposure is mainly from diet and smoking which contains relatively high concentrations of this element.
Cadmium is listed by the US Environmental Protection Agency as one of 126 priority pollutants. In most studies, the half-life of cadmium in humans is estimated to be between 15 and 20 years. It can cause osteoporosis, irreversible renal tubular injury, anemia, eosinophilia, anosmia and chronic rhinitis.
Cadmium is a potent human carcinogen and occupational exposure to it has been associated with cancers of the lung, the prostate, the pancreas, and the kidney. Because of its characteristics as a lung carcinogen, cadmium has been classified as a category 1 carcinogen (human carcinogen) by the International Agency for Research on Cancer and the National Toxicology Program of the USA. Furthermore, an association between human prostate cancer and cadmium was found, but has been considered controversial.
A lot of investigations about the cytotoxicity and carcinogenicity of cadmium were done over the world and those studies for molecular mechanism of cadmium carcinogenicity were paid more attention to, however, the concrete mechanism is still unclear. It has been found that cadmium could cause genetic toxicity directly and indirectly, such as cause DNA strand break, DNA and protein cross-link, oxidative DNA damage and chromatosome anisotrophy, and those genetic toxicities may contribute to carcinogenesis. Cadmium could activate and inactivate many cellular genes and proteins. It was reported that tumor repression gene p53 and proto-oncogenes (c-jun, c-fos and c-myc) could be activated by cadmium. As an important tumor repression gene, p53 could induce apoptosis after DNA damage in mammal cells and involve in DNA repair and cell cycle checkpoint. We employed two methods to
inactivate p53 in order to study what the role p53 play in DNA damage, cell cycle checkpoint, DNA synthesis process.
In comet assay, it has been found that cadmium could induce DNA damage in both p53-efficient and p53-deficient fibroblast cells, and further induce p53-independent rapid G2 checkpoint and p53-dependent delay G2 checkpoint. It also has been demonstrated that cadmium could inhibit DNA synthesis. In different cell stages treated with cadmium, cells in G2/M stages were more sensitive than the cells in G1. It may be suggested that G2/M stage was the target stage of cadmium. Gadd45, as an important protein in G2/M cells transition, may play a key role in the induction of p53- and ATM-independent rapid G2 checkpoint.
Isoflavones, a kind of phytoestrogen, is similar with 17-β estrogen in structure but the estrogen activity is very low. Epidemiological studies, animal experiments and cell culture found that isoflavones could prevent cancer and inhibit the reproduction of cancer cells. The present results showed that isoflavones could inhibit the reproduction of cancer cells. Cell cycle and related genes analyses showed that PTEN may play a key role in the process. In our studies, we found that Isoflavones could antagonize the DNA damage caused by cadmium. It may contribute to its anti-oxidative characteristic. Isoflavones may neutralize the reactive oxygen species caused by cadmium, and it is the important mechanism for isoflavones to prevent cancer.
In summary, cadmium could induce DNA damage and further induce p53-independent rapid G2 checkpoint and p53-dependent delay G2 checkpoint. The DNA damage did not induce apoptosis but induce permanent cell cycle suspension, senescence and death. Some DNA damage cells enter the further cell cycle and the damaged DNA would enter offspring cells. That is an important mechanism for carcinogenicity of cadmium. However, isoflavones could prevent carcinogenicity of cadmium.
镉被美国环境保护署(EPA)列为126个优先考虑的污染物之一，能造成骨质疏松、肾损伤、贫血等。镉是一种致癌物，职业镉接触同肺癌、前列腺癌、胰腺癌和肾癌相关。镉作为肺的致癌物，镉被国际癌症研究机构(IARC)和美国国家毒理学机构(NTP)定义为1类致癌物。
尽管全世界对镉的细胞毒性和致癌性进行了大量的研究，对于其分子机制研究也越来越重视，但是具体的机制并不清楚。有实验研究发现，镉能直接和间接造成基因毒性，例如引起DNA链的断裂、DNA-蛋白交联、氧化DNA损伤和染色体畸形等，这些可能是镉细胞毒性和致癌的重要机制。镉能激活或失活很多细胞因子。有报道肿瘤抑制基因(p53)和原癌基因(c-jun、c-fos和c-myc等)能够被镉激活。作为一个重要的抑癌基因，p53同时也能使哺乳动物细胞DNA损伤后被诱导凋亡，或引起细胞周期阻滞并进行DNA修复等。本课题主要以细胞模型为研究对象；使用两种方法使野生型p53失活，进而研究镉引起野生型p53细胞和p53功能缺陷型细胞的DNA损伤、细胞周期的检查点反应、DNA合成、微卫星突变率、原癌基因表达等的影响。彗星实验表明镉能造成野生p53细胞和p53功能缺陷型细胞的DNA损伤，进一步引起不依赖于p53的速发型G2检查点反应和依赖于p53的迟发型G2检查点反应，还观察到镉能抑制细胞DNA合成。镉对不同细胞周期的细胞进行染毒发现，S期的细胞比G1期的细胞更为敏感，提示S期可能是镉作用于细胞的靶作用期。Gadd45是G2细胞向M期细胞的过渡中发挥调控作用重要的蛋白，镉诱导Gadd45的表达可能是镉引起的速发型G2检查点反应的调控机制，Gadd45的诱导不依赖于p53、ATM。镉诱导的迟发型G2检查点反应依赖于p53但不依赖于ATM。
大豆异黄酮是一种植物雌激素，它的结构同17-β雌二醇相似，但是雌激素样活性很低。流行病学、动物实验和细胞研究发现大豆异黄酮能预防癌症的发生，并能抑制癌细胞的生长和增殖。
通过实验研究发现，大豆异黄酮能保护镉造成的DNA损伤，大豆异黄酮可能通过其抗氧化自由基的作用中和镉产生的氧化自由基而拮抗镉造成的DNA损伤作用。这可能是植物雌激素预防癌症发生一个重要的机制。
研究还发现，大豆异黄酮能抑制癌症细胞的增殖和生长，其抑制癌症细胞的增殖和生长的作用机制和其预防癌症的发生的作用机制不同，细胞周期和相关基因表达研究表明，大豆异黄酮抑制癌症细胞的增殖和生长中，PTEN基因具有重要的作用。
镉能造成细胞的DNA损伤，进一步引起不依赖于p53速发型G2检查点反应和依赖于p53的迟发型G2检查点反应，使部分细胞的细胞周期永久阻滞，进而细胞老化死亡。而没有发生细胞周期阻滞的DNA受损细胞，带着受损的DNA进入子代细胞，这可能是镉诱导癌症发生的一个重要机制，植物雌激素能保护镉造成DNA损伤。
Cadmium, a heavy metal, is a member of group IIb in the periodic table of elements which is present in soils, sediments, air and water. Major occupational exposure occurs in non-ferrous metal smelters, in the production and processing of cadmium, its alloys and compounds and, increasingly, in the recycling of electronic waste. Non-occupational exposure is mainly from diet and smoking which contains relatively high concentrations of this element.
Cadmium is listed by the US Environmental Protection Agency as one of 126 priority pollutants. In most studies, the half-life of cadmium in humans is estimated to be between 15 and 20 years. It can cause osteoporosis, irreversible renal tubular injury, anemia, eosinophilia, anosmia and chronic rhinitis.
Cadmium is a potent human carcinogen and occupational exposure to it has been associated with cancers of the lung, the prostate, the pancreas, and the kidney. Because of its characteristics as a lung carcinogen, cadmium has been classified as a category 1 carcinogen (human carcinogen) by the International Agency for Research on Cancer and the National Toxicology Program of the USA. Furthermore, an association between human prostate cancer and cadmium was found, but has been considered controversial.
A lot of investigations about the cytotoxicity and carcinogenicity of cadmium were done over the world and those studies for molecular mechanism of cadmium carcinogenicity were paid more attention to, however, the concrete mechanism is still unclear. It has been found that cadmium could cause genetic toxicity directly and indirectly, such as cause DNA strand break, DNA and protein cross-link, oxidative DNA damage and chromatosome anisotrophy, and those genetic toxicities may contribute to carcinogenesis. Cadmium could activate and inactivate many cellular genes and proteins. It was reported that tumor repression gene p53 and proto-oncogenes (c-jun, c-fos and c-myc) could be activated by cadmium. As an important tumor repression gene, p53 could induce apoptosis after DNA damage in mammal cells and involve in DNA repair and cell cycle checkpoint. We employed two methods to
inactivate p53 in order to study what the role p53 play in DNA damage, cell cycle checkpoint, DNA synthesis process.
In comet assay, it has been found that cadmium could induce DNA damage in both p53-efficient and p53-deficient fibroblast cells, and further induce p53-independent rapid G2 checkpoint and p53-dependent delay G2 checkpoint. It also has been demonstrated that cadmium could inhibit DNA synthesis. In different cell stages treated with cadmium, cells in G2/M stages were more sensitive than the cells in G1. It may be suggested that G2/M stage was the target stage of cadmium. Gadd45, as an important protein in G2/M cells transition, may play a key role in the induction of p53- and ATM-independent rapid G2 checkpoint.
Isoflavones, a kind of phytoestrogen, is similar with 17-β estrogen in structure but the estrogen activity is very low. Epidemiological studies, animal experiments and cell culture found that isoflavones could prevent cancer and inhibit the reproduction of cancer cells. The present results showed that isoflavones could inhibit the reproduction of cancer cells. Cell cycle and related genes analyses showed that PTEN may play a key role in the process. In our studies, we found that Isoflavones could antagonize the DNA damage caused by cadmium. It may contribute to its anti-oxidative characteristic. Isoflavones may neutralize the reactive oxygen species caused by cadmium, and it is the important mechanism for isoflavones to prevent cancer.
In summary, cadmium could induce DNA damage and further induce p53-independent rapid G2 checkpoint and p53-dependent delay G2 checkpoint. The DNA damage did not induce apoptosis but induce permanent cell cycle suspension, senescence and death. Some DNA damage cells enter the further cell cycle and the damaged DNA would enter offspring cells. That is an important mechanism for carcinogenicity of cadmium. However, isoflavones could prevent carcinogenicity of cadmium.
引文
[1] IARC, Cadmium and cadmium compounds, IARC Monogr. Eval. Carcinog. Risks Hum., 1993, pp.119-237.
[2] Dally H, Hartwig A. Induction and repair inhibition of oxidative DNA damage by nickel(Ⅱ) and cadmium(Ⅱ) in mammalian cells [J], Carcinogenesis. 1997, 18: 1021-1026.
[3] Hartwig A, Current aspects in metal genotoxicity [J]. Biometals. 1995, 8: 3-11.
[4] Misra, RR, Smith, GT, Waalkes, MP. Evaluation of the genotoxic potential of cadmium in four different rodent cell lines [J]. Toxicology. 1998, 126: 103-114
[5] Andrews GK, Harding MA, Calvet JP et al. The heat shock response in HeLa cells is accompanied by elevated expression of the c-fos proto-oncogene [J], Mol. Cell. Biol. 1987, 7; 3452-3458.
[6] Jin P, Ringertz N. Cadmium induces transcription ofprotooncogenes c-jun and c-myc in rat L6 myoblasts [J], J. Biol. Chem. 1990, 265: 14061-14064.
[7] Zheng H, Liu J, Choo KH et al. Metallothionein-Ⅰ and -Ⅱ knock-out mice are sensitive to cadmium-induced liver mRNA expression ofc-jun and p53 [J], Toxicol. Appl. Pharmacol. 1996, 136: 229-235
[8] Adlercreutz H, Mazur W, Bartels P, et al. Phytoestrogens and prostate disease [J]. J Nutr, 2000, 130 (3): 658-659.
[9] Stephens FO. Phytoestrogens and prostate cancer: possible preventive role [J]. Med J Australia, 1997, 167: 138-140.
[10] Chmielnicka J, Cherian MG, Environmental exposure to cadmium and factors affecting trace-metal metabolism and metal toxicity [J], Biol. Trace Elem. Res. 1986, 10: 243-256
[11] Waalkes M, Coogan PTP, Batter RA. Toxicological principles of metal carcinogenesis with special emphasis on cadmium [J], Cric. Rev. Toxicol. 1992, 22: 175-201
[12] Hassoun EA, Stohs SJ. Cadmium-induced production of superoxide anion and nitric oxide, DNA single strand breaks and lactate dehydrogenase leakage in J774A. 1 cell cultures [J]. Toxicology 1996, 112(3): 219-226.
[13] Fotakis G, Cemeli E, Anderson D et al. Cadmium chloride-induced DNA and lysosomal damage in a hepatoma cell line[J]. Toxicol In Vitro 2005, 19(4): 481-489.
[14] Kastan MB, Bartek J. Cell-cycle checkpoints and cancer [J]. Nature 2004, 432(7015): 316-323.
[15] Sancar A, Lindsey-Boltz LA, Unsal-Kaccmaz K et al. Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints [J]. Annu Rev Biochem 2004, 73: 39-85.
[16] Bakkenist CJ, Kastan MB: DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J]. Nature 2003, 421 (6922): 499-506
[17] Agarwal ML, Taylor WR, Chernov MV et al. The p53 network. J Biol Chem. 1998, 273(1): 1-4.
[18] Malkin D, Li FP, Strong LC et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms [J]. Science. 1990, 250(4985): 1233-1238.
[19] Savitsky K, Bar-Shira A, Gilad Set al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase [J]. Science. 1995,268(5218): 1749-1753.
[20] Maher VM, McCormick JJ. Effect of DNA repair on the cytotoxicity and mutagenicity of UV irradiation and of chemical carcinogens in normal and xeroderma pigmentosum cells [J]. Biology of radiation carcinogensis 1976, 48: 129-45.
[21] Boyer JC, Kaufmann WK, Cordeiro-Stone M. Role of postreplication repair in transformation of human fibroblasts to anchorage independence [J]. Cancer Res. 1991, 51(11):2960-2964.
[22] Deming PB, Flores KG, Dowries CS et al. ATR enforces the topoisomerase II-dependent G2 checkpoint through inhibition of Plk1 kinase [J]. J Biol Chem. 2002, 277(39):36832-36838.
[23] Heffernan TP, Simpson DA, Frank AR et al. An ATR- and Chk1 -dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage [J]. Mol Cell Biol. 2002, 22(24):8552-8561.
[24] Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning [M], A Laboratory Manual. 1989.
[25] Simpson DA, Livanos E, Heffernan TP et al. Telomerase Expression is Sufficient for Chromosomal Integrity in Cells Lacking p53 Dependent G1 Checkpoint Function [J]. J Carcinog 2005, 4(1): 18-25.
[26] Comstock KE, Watson NF, Olsen JC. Design of retroviral expression vectors [J]. Methods Mol Biol. 1997, 62:207-222.
[27] Johnson LG, Mewshaw JP, Ni H et al. Effect of host modification and age on airway epithelial gene transfer mediated by a murine leukemia virus-derived vector [J]. J Virol. 1998, 72(11):8861-8872.
[28] Olsen JC, Johnson LG, Wong-Sun ML et al. Retrovirus-mediated gene transfer to cystic fibrosis airway epithelial cells: effect of selectable marker sequences on long-term expression [J]. Nucleic Acids Res. 1993, 21(3):663-669.
[29] Kaufmann WK, Heffernan TP, Beaulieu LM, et al. Caffeine and human DNA metabolism: the magic and the mystery [J]. Mutat Res 2003, 532:85-102.
[30] Linzer DI, Levine AJ. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells [J].Cell. 1979, 17(1):43-52.
[31] Hollstein M, Sidransky D, Vogelstein B et al. p53 mutations in human cancers [J]. Science. 1991, 253(5015):49-53.
[32] Hall PA, Lane DP. p53 in tumour pathology: can we trust immunohistochemistry? -- Revisited! [J] J Pathol. 1994, 172(1): 1-4.
[33] Lane DP. Cancer. p53, guardian of the genome [J]. Nature. 1992, 358(6381):15-6.
[34] Tishler RB, Calderwood SK, Coleman CN et al. Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents [J]. Cancer Res. 1993, 53(10 Suppl):2212-6.
[35] Reed M, Woelker B, Wang P et al. The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation [J]. Proc Natl Acad Sci U S A. 1995, 92(21):9455-9.
[36] Woo RA, McLure KG, Lees-Miller SP et al. DNA-dependent protein kinase acts upstream of p53 in response to DNA damage [J]. Nature. 1998, 394(6694):700-4.
[37] Shieh SY, Ikeda M, Taya Y et al. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2 [J]. Cell. 1997, 91(3):325-34.
[38] Robert T. Cell cycle checkpoint signaling through the ATM and ATR kinases [J]. Genes & Development. 15:2177-2196
[39] Kaufmann WK, Wilson SJ. DNA repair endonuclease activity during synchronous growth of diploid human fibroblasts [J]. Mutat Res 1990, 236(1):107-117.
[40] Cordeiro-Stone M, Boyer JC, Smith BA et al. Effect of benzo[a]pyrene-diol-epoxide-I on growth of nascent DNA in synchronized human fibroblasts [J]. Carcinogenesis 1986, 7(10):1775-1781.
[41] Juan G, Traganos F, James WM et al. Histone H3 phosphorylation and expression of cyclins A and B1 measured in individual cells during their progression through G2 and mitosis [J]. Cytometry. 1998, 32(2):71-77.
[42] Sasaki YF, Izumiyama F, Nishidate E et al. Simple detection of in vivo genotoxicity of pyrimethamine in rodents by the modified alkaline single-cell gel electrophoresis assay [J]. Mutat Res. 1997, 392(3):251-259.
[43] Jin T, Nordberg G, Ye T, et al. Osteoporosis and renal dysfunction in a general population exposed to cadmium in China [J]. Environ Res. 2004, 96:353-9.
[44] Jin T, Kong Q, Ye T, et al. Renal dysfunction of cadmium-exposed workers residing in a cadmium-polluted environment [J]. Biometals, 2004, 17:513-8.
[45] Navarrete M H , Carrera P , Miguel M, et al. A fast comet assay variant for solid tissue cells. The assessment of DNA damage in higher plants [J ] . Mutat Res. 1997 , 389: 271-277
[46] Mouron SA, Grillo CA, Dulout FN, et al. A comparative investigation of DNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells [J]. Mutat Res, 2004, 568:221-231.
[47] Fatur T, Lah TT, Filipic M. Cadmium inhibits repair of UV-, methyl methanesulfonate- and N-methyl-N-nitrosourea-induced DNA damage in Chinese hamster ovary cells [J]. Mutat Res, 2003, 529:109-116.
[48] Lopez-Ortal P, Souza V, Bucio L, et al. DNA damage produced by cadmium in a human fetal hepatic cell line [J]. Mutat Res. 1999, 439:301-306.
[49] Amoruso MA, Witz G, Goldstein BF. Enhancement of rat and human phagocyte superoxide anion radical production by cadmium in vitro [J]. Toxicology Letters, 1982, 10:133-138.
[50] De Faverney CR, Lafaurie M, Girard JP, et al. The nitroxide stable radical tempo prevents metal-induced inhibition of CYP1A1 expression and induction [J]. Toxicology Letters, 2000, 111:219-227.
[51] Hwua YS, Yang JL. Effect of 3-aminotriazole on anchorage independence and mutagenicity in cadmium- and lead-treated diploid human fibroblasts [J]. Carcinogenesis, 1998, 19(5):881-888.
[52] Latinwo LM, Ikediobi CO, Singh NP, et al. Comparative studies of in vivo genotoxic effects of cadmium chloride in rat brain, kidney and liver cells [J]. Cell Mol. Biol., 1997,43:203-210.
[53] Valverde M, Fortoul TI, Diaz-Barriga F, et al. Induction of genotoxicity by cadmium chloride inhalation in several organs of CD-I mice [J]. Mutagenesis, 2000, 15:109-114.
[54] Lakin ND, Jackson SP. Regulation of p53 in response to DNA damage [J]. Oncogene, 1999 13;18(53):7644-55.
[55] Taylor WR, Stark GR. Regulation of the G2/M transition by p53 [J]. Oncogene, 2001,20: 1803-1815
[56] Xu B, Kim ST, Lim DS et al. Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation [J]. Mol Cell Biol., 2002, 22(4): 1049-59.
[57] Brown EJ, Baltimore D. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance [J]. Genes Dev. 2003, 17(5):615-28.
[58] Lakin ND, Jackson SP. Regulation of p53 in response to DNA damage [J]. Oncogene. 1999 13;18(53):7644-55.
[59] Cistulli CA, Kaufmann WK. p53-dependent signaling sustains DNA replication and enhances clonogenic survival in 254 nm ultraviolet-irradiated human fibroblasts [J]. Cancer Research, 1998, 58(9): 1993-2002.
[60] Cordeiro-Stone M, Frank A, Bryant M et al. DNA damage responses protect xeroderma pigmentosum variant from UVC-induced clastogenesis [J]. Carcinogenesis, 2002, 23(6):959-965.
[61] Pardee AB. Regulation, restriction, and reminiscences [J]. J Biol Chem., 2002, 277(30):26709-16.
[62] Paulovich AG, Hartwell LH. A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage [J]. Cell. 1995, 82(5):841-7.
[63] Dunphy, W. G. (1994). The decision to enter mitosis [J]. Trends Cell Biol. 4, 202-207.
[64] Mueller, P. R., Coleman, T. R., Kumagai, A et al. Mytl: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15 [J]. Science, 1995,270,86-90.
[65] Fleck, O. and Nielsen, O. DNA repair [J]. J. Cell Sci. 2004, 117: 515-517.
[66] Zhao H, Piwnica-Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1 [J]. Mol Cell Biol. 2001, 21(13):4129-39.
[67] Shiloh Y. Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart [J]. Annu Rev Genet. 1997, 31:635-62.
[68] Banin S, Moyal L, Shieh S et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage [J]. Science. 1998, 281(5383):1674-7.
[69] Gately DP, Hittle JC, Chan GK et al. Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity [J]. Mol Biol Cell. 1998,9(9):2361-74.
[70] Chan DW, Son SC, Block W et al. Purification and characterization of ATM from human placenta. A manganese-dependent, wortmannin-sensitive serine/threonine protein kinase [J]. J Biol Chem. 2000, 275(11):7803-10.
[71] Canman CE, Lim DS, Cimprich KA et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 [J]. Science. 1998, 281(5383):1677-9.
[72] Lim DS, Kim ST, Xu B et al. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway [J]. Nature. 2000, 404(6778):613-7.
[73] Cortez D, Wang Y, Qin J et al. Requirement of ATM-dependent phosphorylation of brcal in the DNA damage response to double-strand breaks [J]. Science. 1999, 286(5442): 1162-6.
[74] Kaufmann WK, Paules RS. DNA damage and cell cycle checkpoints [J]. FASEB Journal, 1996, 10(2):238-247.
[75] Melo J, Toczyski D et al. A unified view of the DNA-damage checkpoint [J]. Curr Opin Cell Biol, 2002, 14(2):237-245.
[76] Osborn AJ, Elledge SJ, Zou L. Checking on the fork: the DNA-replication stress-response pathway [J]. Trends Cell Biol, 2002, 12(11):509-516.
[77] Abraham RT. Cell cycle checkpoint signaling through the ATM and ATR kinases [J]. Genes Dev, 2001, 15(17):2177-2196.
[78] Wang XW, Zhan Q, Coursen JD et al. GADD45 induction of a G2/M cell cycle checkpoint [J]. Proc Natl Acad Sci, 1999, 96(7):3706-3711.
[79] Yang Q, Manicone A, Coursen JD et al. Identification of a Functional Domain in a GADD45-mediated G2/M Checkpoint [J]. J Biol Chem 2000, 275(47): 36892 - 36898.
[80] Zhan Q, Antinore MJ, Wang XW et al. Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45 [J]. Oncogene, 1999, 18(18):2892-2900.
[81] Banin S, Moyal L, Shieh S et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage [J]. Science, 1998, 281(5383): 1674-1677.
[82] Ryan KM, Phillips AC, Vousden KH. Regulation and function of the p53 tumor suppressor protein [J]. Curr Opin Cell Biol, 2001, 13(3):332-337.
[83] Zhang Y, Xiong Y. Ap53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation [J]. Science, 2001, 292(5523):1910-1915.
[84] Matsuoka M, Igisu H. Cadmium induces phosphorylation of p53 at serine 15 in MCF-7 cells [J]. Biochem Biophys Res Commun, 2001, 282(5): 1120-1125.
[85] Meplan C, Mann K, Hainaut P. Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells [J]. J Biol Chem, 1999, 274(44):31663-31670.
[86] Mukherjee JJ, Gupta SK, Kumar S et al. Effects of cadmium(II) on (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-induced DNA damage response in human fibroblasts and DNA repair: a possible mechanism of cadmium's cogenotoxicity [J]. Chem Res Toxicol, 2004, 17(3):287-293.
[87] Leach SD, Scatena CD, Keefer CJ et al. Negative regulation of Weel expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis [J]. Cancer Res, 1998, 58(15):3231-3236.
[88] Passalaris TM, Benanti JA, Gewin L et al. The G(2) checkpoint is maintained byredundant pathways [J]. Mol Cell Biol, 1999, 19(9):5872-5881.
[89] Deming PB, Cistulli CA, Zhao H et al. The human decatenation checkpoint [J]. Proc Natl Acad Sci, 2001, 98(21): 12044-12049.
[90] Banfalvi G, Littlefield N, Hass B et al. Effect of cadmium on the relationship between replicative and repair DNA synthesis in synchronized CHO cells [J]. Eur J Biochem., 2000, 267(22):6580-6585.
[91] Von Zglinicki T, Edwall C, Ostlund E et al. Very low cadmium concentrations stimulate DNA synthesis and cell growth [J]. J Cell Sci, 1992, 103:1073-1081.
[92] Waalkes MP. Cadmium carcinogenesis [J]. Mutat Res, 2003, 533(1-2): 107-120.
[93] Beyersmann D, Hechtenberg S. Cadmium, gene regulation, and cellular signalling in mammalian cells[J]. Toxicol Appl Pharmacol, 1997, 144(2):247-261.
[94] Nocentini S. Inhibition of DNA replication and repair by cadmium in manmmalian cells. Protective interaction of zinc [J]. Nucleic Acids Research. 1987, 15(10): 4211-4225.
[95] Popenoe EA, Schmaeler MA. Interaction of human DNA polymerase beta with ions of copper, lead, and cadmium [J]. Arch Biochem Biophys., 1979, 196(1): 109-20..
[96] Prasad AS, Oberleas D. Thymidine kinase activity and incorporation of thymidine into DNA in zinc-deficient tissue [J]. J Lab Clin Med., 1974, 83(4):634-9.
[97] Clark AB, Kunkel TA, Cadmium inhibits the functions of eukaryotic MutS complexes [J]. J Biol Chem 2004, 279(52):53903-53906.
[98] Falck J, Mailand N, Syljuasen RG et al. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis [J]. Nature 2001, 410 (6830): 842-847.
[99] Dimri GP, Lee X, Basile G et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo [J]. Proc. Natl Acad. Sci. 1995, 92: 9363 - 9367.
[100] Wang Y, Meng A, Zhou D. Inhibition of phosphatidylinostol 3-kinase uncouples H2O2-induced senescent phenotype and cell cycle arrest in normal human diploid fibroblasts [J]. Exp Cell Res., 2004, 298:188-96.
[101] Marcotte R, Wang E. Replicative senescence revisited [J]. A Biol. Sci. Med. Sci., 2002, 57: B257-B269.
[102] Serrano M, Blasco MA. Putting the stress on senescence [J], Curr. Opin. Cell Biol., 2001, 13:748-753
[103] Serrano M, Blasco MA. Putting the stress on senescence [J], Curr. Opin. Cell Biol., 2001, 13:748-753
[104] Boyer JC, Yamada NA, Roques CN et al. Sequence dependent instability of mononucleotide microsatellites in cultured mismatch repair proficient and deficient mammalian cells [J]. Hum Mol Genet 2002, 11(6):707-713.
[105] Yamada NA, Castro A, Farber RA. Variation in the extent of microsatellite instability in human cell lines with defects in different mismatch repair genes [J]. Mutagenesis, 2003, 18(3):277-282.
[106] Luria SF, Delbruck M. Mutations of bacteria from virus sensitivity to virus resistance[J]. Genetics, 1943, 28:491-511.
[107] Capizzi RL, Jameson JW. A table for the estimation of the spontaneous mutation rate of cells in culture [J]. Mutat Res., 1973, 17(1):147-148.
[108] Yamada NA, Parker JM, Farber RA. Mutation frequency analysis of mononucleotide and dinucleotide repeats after oxidative stress [J]. Environ Mol Mutagen 2003, 42(2):75-84.
[109] Mark J. S and Peggy H. DNA mismatch repair molecular mechanisms and biological function [J]. Annu. Rev. Microbiol., 2003. 57:579-608
[110] Banerjee S, Flores-Rozas H. Cadmium inhibits mismatch repair by blocking the ATPase activity of the MSH2-MSH6 complex [J]. Nucleic Acids Res., 2005, 33 (4): 1410-1419.
[111] Bacon AL, Farrington SM, Dunlop MG. Mutation frequency in coding and non-coding repeat sequences in mismatch repair deficient cells derived from normal human tissue [J]. Oncogene, 2001, 20(51):7464-7471.
[112] Jin YH, Clark AB, Slebos RJ et al. Cadmium is a mutagen that acts by inhibiting mismatch repair [J]. Nat Genet., 2003, 34(3):326-329.
[113] Griffiths K, Morton MS, Denis L. Certain aspects of molecular endocrinology that relate to the influence of dietary factors on the pathogenesis of prostate cancer [J]. Eur Urol, 1999,35:443-55
[114] Tham DM, Gardner CD, Haskel WL. Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence [J]. J Clin Endocrinol Metab, 198, 83: 2223-2235.
[115] Schleicher RL, Lamartiniere CA, Zheng M, et al .The inhibitory effect of genistein on the growth and metastasis of a transplantable rat accessory sex gland carcinoma [J]. Cancer Lett., 1999 ,136(2):195-201.
[116] Zhou JR, Gugger ET, Tanaka T, et al. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice [J].JNutr,1999,129(9): 1628-35.
[117] Suzuki K, Koike H, Matsui H, et al. Genistein, a soy isoflavone. induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3 [J]. Int J Cancer, 2002 ,99(6):846-52.
[118] Kuiper GGJM, Enmark E, Pelto-Huikko M, et al. Cloning of a novel estrogen receptor expressed in rat prostate and ovary [J]. Proc Natl Acad Sci USA, 1996, 93: 5925-5930.
[119] Laura S, Ramon P. PTEN: Life as a Tumor Suppressor Experimental [J]. Cell Resesrch, 2001, 264: 29-41
[120] Koul D , Shen R, Garyali A, et al. MMAC/PTEN tumor suppressor gene regulates vascular endothelial growth factor-mediated angiogenesis in prostate cancer [J]. Int J Oncol, 2002 , 21(3): 469-75
[121] Ming HZ, Jiake X, Peter R, et al. Gene expression of vascular endothelial growth factor in giant cell tumors of bone [J]. Human Pathology, 2000, 31: 804-812
[122] Kazuko S. Synergistic effects of thearubigin and genistein on human prostate tumor cell (PC-3) growth via cell cycle arrest [J]. Cancer Letters, 2000, 151: 103-109
[123] Takashi K, Teruhiro N, Takejiro K. Effect of fiavonoids on cell cycle progression in prostate cancer cells [J]. Cancer Letters, 2002, 176: 17-23
[124] Grunwald V, DeGraffenried L, Russel D, et al. Inhibitors of mTOR Reverse Doxorubicin Resistance Conferred by PTEN Status in Prostate Cancer Cells [J]. Cancer Resesrch, 2002, 62: 6141-6145
[125] Mitchell JH, Duthie SJ, Collins AR. Effects of phytoestrogens on growth and DNA integrity in human prostate tumor cell lines: PC-3 and LNCaP [J]. Nutr Cancer, 2000, 38(2): 223-8
[126] Kazuhiro S, Hidekazu K, Hiroshi M. Genistein, a soy isoflavone,induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3 [J]. Int. J Cancer, 2002, 99: 846-852
[127] Davis J.N, Singh B,Bhuiyan M, et al. Genistein-induced upregulation of p21 WAF1,downregulation of cyclin B, and induction of apoptosis in prostate cancer cells [J]. Nutr. Cancer, 1998, 32: 123-131
[128] Cotroneo MS, Wang W, Eltoum IE, et al. Sex steroid receptor regulation by genistein in the prepubertal rat uterus [J]. Mol. Cell. Endocrinol, 2001, 173: 135-145.
[129] Denis L, Morton MS, Griffiths K. Diet and its preventive role in prostatic disease [J]. Eur Urol, 1999, 35: 377-387
[130] Lamartiniere CA, Cotroneo MS, Fritz WA, et al. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate [J]. J Nutr, 2002, 132(3): 552S-558S
[131] Prins GS, Birch L. Neonatal estrogen exposure up-regulates estrogen receptor expression in the developing and adult rat prostate lobes [J]. Endocrinology, 1997, 138: 1801-1809.
[132] Klein KO. Isoflavones, soy-based infant formulas, and relevance to endocrine function [J]. Nutr. Rev, 1998, 56: 193-204.
[133] Strauss L, Makela S, Joshi S, et al. Genistein exerts estrogen-like effects in male mouse reproductive tract [J]. Mol. Cell. Endocrinol, 1998, 144: 83-93.
[134] Bektic J, Berger AP, Pfeil K, et al. Androgen receptor regulation by physiological concentrations of the isoflavonoid genistein in androgen-dependent LNCaP cells is mediated by estrogen receptor beta [J]. Eur Urol, 2004, 45(2): 245-51
[135] Li P, Yu X, Ge K, et al. Heterogeneous expression and functions of androgen receptor co-factors in primary prostate cancer [J]. Am J Pathol, 2002, 161: 1467-74
[136] Manju S, William WC, Zijie S. Phosphatidylinositol 3-Kinase/Akt Stimulates Androgen Pathway through GSK3P Inhibition and Nuclear P-Catenin Accumulation [J]. The Journal of Biological Chemistry, 2002, 277: 30935-30941.
[137] Pumford SL, Morton MM, Turkes A et al.Determination of the isoflavonoids genistein and daidzein in biological samples by gas chromatography-mass spectrometry [J]. Ann Clin Bio chem, 2002, 39(3):281-292.
[138] Strom S,Yamamura Y, Duphorne CM et al. Phytoestrogen intake and prostate cancer: a case-control study using a new database [J]. Nut Cancer, 1999, 33 (11):20-25.
[139] Kirk P, Patterson RE, Lampe J. Development of a soy food frequency questionnaire to estimate isoflavone consumption in US adults [J]. J Am Diet Assoc, 1999,99:558-563.
[140] Chen Z, Zheng W, Custer LJ et al. Usual dietary consumption of soy foods ant its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai [J]. Nutr Cancer, 199, 33: 82-87.
[141] Wakai K, Egami I, Kato K et al. Dietary intake and sources of isoflavone among Japanese [J]. Nutr Cancer, 1999, 33: 139-145.
[142] Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence [J]. Cancer Cause Control, 1998, 9: 553-557.
[1] Adlercreutz H, Mazur W, Bartels P et al. Phytoestrogens and Prostate Disease [J]. Journal of Nutrition, 2000,130:658S-659S.
[2] Griffiths K, Morton MS, Denis L. Certain aspects of molecular endocrinology that relate to the influence of dietary factors on the pathogenesis of prostate cancer [J]. Eur Urol,1999,35(5-6):443-55.
[3] Strom SS, Yamamura Y, Duphorne CM et al . Phytoestrogen intake and prostate cancer: a case-control study using a new database [J]. Nutr Cancer, 1999,33(1):20-5.
[4] Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study [J]. Cancer Causes Control, 1998,9(6):553-7.
[5] Schleicher RL, Lamartiniere CA, Zheng M et al .The inhibitory effect of genistein on the growth and metastasis of a transplantable rat accessory sex gland carcinoma. Cancer Lett 1999 ,136(2):195-201.
[6] Zhou JR, Gugger ET, Tanaka T et al. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice [J]. J Nutr,1999,129(9):1628-35.
[7] Lamartiniere CA, Cotroneo MS, Fritz WA et al. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate [J]. J Nutr ,2002 ,132(3):552S-558S.
[8] Pollard M, Wolter W. Prevention of spontaneous prostate-related cancer in Lobund-Wistar rats by a soy protein isolate/isoflavone diet [J]. Prostate, 2000,45(2):101-5.
[9] Geller J, Sionit L, Partido C et al. Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture [J] Prostate, 1998,34(2):75-9.
[10] Suzuki K, Koike H, Matsui H et al. Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3 [J]. Int J Cancer, 2002 ,99(6):846-52.
[11] Mitchell JH, Duthie SJ, Collins AR. Effects of phytoestrogens on growth and DNA integrity in human prostate tumor cell lines: PC-3 and LNCaP [J]. Nutr Cancer, 2000,38(2):223-8.
[12] Weber KS, Setchell KD, Stocco DM et al . Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats [J]. J Endocrinol, 2001,170(3):591-9.
[13] Sun XY, Plouzek CA, Henry JP et al. Increased UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells [J]. Cancer Res, 1998,58(11):2379-84.
[14] Dalu A, Haskell JF, Coward L, et al. Genistein, a component of soy, inhibits the expression of the EGF and ErbB2/Neu receptors in the rat dorsolateral prostate [J]. Prostate, 1998 ,37(1):36-43.
[15] Peterson G, Barnes S. Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation [J]. Prostate, 1993,22(4):335-45.
[16] Davis JN, Singh B, Bhuiyan M et al. Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells [J]. Nutr Cancer, 1998,32(3):123-31.
[17] Onozawa M, Fukuda K, Ohtani M et al. Effects of soybean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP [J]. Jpn J Clin Oncol ,1998,28(6):360-3.
[18] Shen JC, Klein RD, Wei Q et al. Low-dose genistein induces cyclin-dependent kinase inhibitors and G(1) cell-cycle arrest in human prostate cancer cells [J]. Mol Carcinog, 2000,29(2):92-102.
[20] Kumi-Diaka J, Sanderson NA, Hall A. The mediating role of caspase-3 protease in the intracellular mechanism of genistein-induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP [J]. Biol Cell, 2000,92(8-9):595-604.
[21] Bhatia N, Agarwal R. Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145. cells [J]. Prostate, 2001,46(2):98-107.
[22] Bergan R, Kyle E, Nguyen P, et al. Genistein-stimulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-1-integrin [J]. Clin Exp Metastasis, 1996,14(4):389-98.
[2] Dally H, Hartwig A. Induction and repair inhibition of oxidative DNA damage by nickel(Ⅱ) and cadmium(Ⅱ) in mammalian cells [J], Carcinogenesis. 1997, 18: 1021-1026.
[3] Hartwig A, Current aspects in metal genotoxicity [J]. Biometals. 1995, 8: 3-11.
[4] Misra, RR, Smith, GT, Waalkes, MP. Evaluation of the genotoxic potential of cadmium in four different rodent cell lines [J]. Toxicology. 1998, 126: 103-114
[5] Andrews GK, Harding MA, Calvet JP et al. The heat shock response in HeLa cells is accompanied by elevated expression of the c-fos proto-oncogene [J], Mol. Cell. Biol. 1987, 7; 3452-3458.
[6] Jin P, Ringertz N. Cadmium induces transcription ofprotooncogenes c-jun and c-myc in rat L6 myoblasts [J], J. Biol. Chem. 1990, 265: 14061-14064.
[7] Zheng H, Liu J, Choo KH et al. Metallothionein-Ⅰ and -Ⅱ knock-out mice are sensitive to cadmium-induced liver mRNA expression ofc-jun and p53 [J], Toxicol. Appl. Pharmacol. 1996, 136: 229-235
[8] Adlercreutz H, Mazur W, Bartels P, et al. Phytoestrogens and prostate disease [J]. J Nutr, 2000, 130 (3): 658-659.
[9] Stephens FO. Phytoestrogens and prostate cancer: possible preventive role [J]. Med J Australia, 1997, 167: 138-140.
[10] Chmielnicka J, Cherian MG, Environmental exposure to cadmium and factors affecting trace-metal metabolism and metal toxicity [J], Biol. Trace Elem. Res. 1986, 10: 243-256
[11] Waalkes M, Coogan PTP, Batter RA. Toxicological principles of metal carcinogenesis with special emphasis on cadmium [J], Cric. Rev. Toxicol. 1992, 22: 175-201
[12] Hassoun EA, Stohs SJ. Cadmium-induced production of superoxide anion and nitric oxide, DNA single strand breaks and lactate dehydrogenase leakage in J774A. 1 cell cultures [J]. Toxicology 1996, 112(3): 219-226.
[13] Fotakis G, Cemeli E, Anderson D et al. Cadmium chloride-induced DNA and lysosomal damage in a hepatoma cell line[J]. Toxicol In Vitro 2005, 19(4): 481-489.
[14] Kastan MB, Bartek J. Cell-cycle checkpoints and cancer [J]. Nature 2004, 432(7015): 316-323.
[15] Sancar A, Lindsey-Boltz LA, Unsal-Kaccmaz K et al. Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints [J]. Annu Rev Biochem 2004, 73: 39-85.
[16] Bakkenist CJ, Kastan MB: DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J]. Nature 2003, 421 (6922): 499-506
[17] Agarwal ML, Taylor WR, Chernov MV et al. The p53 network. J Biol Chem. 1998, 273(1): 1-4.
[18] Malkin D, Li FP, Strong LC et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms [J]. Science. 1990, 250(4985): 1233-1238.
[19] Savitsky K, Bar-Shira A, Gilad Set al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase [J]. Science. 1995,268(5218): 1749-1753.
[20] Maher VM, McCormick JJ. Effect of DNA repair on the cytotoxicity and mutagenicity of UV irradiation and of chemical carcinogens in normal and xeroderma pigmentosum cells [J]. Biology of radiation carcinogensis 1976, 48: 129-45.
[21] Boyer JC, Kaufmann WK, Cordeiro-Stone M. Role of postreplication repair in transformation of human fibroblasts to anchorage independence [J]. Cancer Res. 1991, 51(11):2960-2964.
[22] Deming PB, Flores KG, Dowries CS et al. ATR enforces the topoisomerase II-dependent G2 checkpoint through inhibition of Plk1 kinase [J]. J Biol Chem. 2002, 277(39):36832-36838.
[23] Heffernan TP, Simpson DA, Frank AR et al. An ATR- and Chk1 -dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage [J]. Mol Cell Biol. 2002, 22(24):8552-8561.
[24] Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning [M], A Laboratory Manual. 1989.
[25] Simpson DA, Livanos E, Heffernan TP et al. Telomerase Expression is Sufficient for Chromosomal Integrity in Cells Lacking p53 Dependent G1 Checkpoint Function [J]. J Carcinog 2005, 4(1): 18-25.
[26] Comstock KE, Watson NF, Olsen JC. Design of retroviral expression vectors [J]. Methods Mol Biol. 1997, 62:207-222.
[27] Johnson LG, Mewshaw JP, Ni H et al. Effect of host modification and age on airway epithelial gene transfer mediated by a murine leukemia virus-derived vector [J]. J Virol. 1998, 72(11):8861-8872.
[28] Olsen JC, Johnson LG, Wong-Sun ML et al. Retrovirus-mediated gene transfer to cystic fibrosis airway epithelial cells: effect of selectable marker sequences on long-term expression [J]. Nucleic Acids Res. 1993, 21(3):663-669.
[29] Kaufmann WK, Heffernan TP, Beaulieu LM, et al. Caffeine and human DNA metabolism: the magic and the mystery [J]. Mutat Res 2003, 532:85-102.
[30] Linzer DI, Levine AJ. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells [J].Cell. 1979, 17(1):43-52.
[31] Hollstein M, Sidransky D, Vogelstein B et al. p53 mutations in human cancers [J]. Science. 1991, 253(5015):49-53.
[32] Hall PA, Lane DP. p53 in tumour pathology: can we trust immunohistochemistry? -- Revisited! [J] J Pathol. 1994, 172(1): 1-4.
[33] Lane DP. Cancer. p53, guardian of the genome [J]. Nature. 1992, 358(6381):15-6.
[34] Tishler RB, Calderwood SK, Coleman CN et al. Increases in sequence specific DNA binding by p53 following treatment with chemotherapeutic and DNA damaging agents [J]. Cancer Res. 1993, 53(10 Suppl):2212-6.
[35] Reed M, Woelker B, Wang P et al. The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation [J]. Proc Natl Acad Sci U S A. 1995, 92(21):9455-9.
[36] Woo RA, McLure KG, Lees-Miller SP et al. DNA-dependent protein kinase acts upstream of p53 in response to DNA damage [J]. Nature. 1998, 394(6694):700-4.
[37] Shieh SY, Ikeda M, Taya Y et al. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2 [J]. Cell. 1997, 91(3):325-34.
[38] Robert T. Cell cycle checkpoint signaling through the ATM and ATR kinases [J]. Genes & Development. 15:2177-2196
[39] Kaufmann WK, Wilson SJ. DNA repair endonuclease activity during synchronous growth of diploid human fibroblasts [J]. Mutat Res 1990, 236(1):107-117.
[40] Cordeiro-Stone M, Boyer JC, Smith BA et al. Effect of benzo[a]pyrene-diol-epoxide-I on growth of nascent DNA in synchronized human fibroblasts [J]. Carcinogenesis 1986, 7(10):1775-1781.
[41] Juan G, Traganos F, James WM et al. Histone H3 phosphorylation and expression of cyclins A and B1 measured in individual cells during their progression through G2 and mitosis [J]. Cytometry. 1998, 32(2):71-77.
[42] Sasaki YF, Izumiyama F, Nishidate E et al. Simple detection of in vivo genotoxicity of pyrimethamine in rodents by the modified alkaline single-cell gel electrophoresis assay [J]. Mutat Res. 1997, 392(3):251-259.
[43] Jin T, Nordberg G, Ye T, et al. Osteoporosis and renal dysfunction in a general population exposed to cadmium in China [J]. Environ Res. 2004, 96:353-9.
[44] Jin T, Kong Q, Ye T, et al. Renal dysfunction of cadmium-exposed workers residing in a cadmium-polluted environment [J]. Biometals, 2004, 17:513-8.
[45] Navarrete M H , Carrera P , Miguel M, et al. A fast comet assay variant for solid tissue cells. The assessment of DNA damage in higher plants [J ] . Mutat Res. 1997 , 389: 271-277
[46] Mouron SA, Grillo CA, Dulout FN, et al. A comparative investigation of DNA strand breaks, sister chromatid exchanges and K-ras gene mutations induced by cadmium salts in cultured human cells [J]. Mutat Res, 2004, 568:221-231.
[47] Fatur T, Lah TT, Filipic M. Cadmium inhibits repair of UV-, methyl methanesulfonate- and N-methyl-N-nitrosourea-induced DNA damage in Chinese hamster ovary cells [J]. Mutat Res, 2003, 529:109-116.
[48] Lopez-Ortal P, Souza V, Bucio L, et al. DNA damage produced by cadmium in a human fetal hepatic cell line [J]. Mutat Res. 1999, 439:301-306.
[49] Amoruso MA, Witz G, Goldstein BF. Enhancement of rat and human phagocyte superoxide anion radical production by cadmium in vitro [J]. Toxicology Letters, 1982, 10:133-138.
[50] De Faverney CR, Lafaurie M, Girard JP, et al. The nitroxide stable radical tempo prevents metal-induced inhibition of CYP1A1 expression and induction [J]. Toxicology Letters, 2000, 111:219-227.
[51] Hwua YS, Yang JL. Effect of 3-aminotriazole on anchorage independence and mutagenicity in cadmium- and lead-treated diploid human fibroblasts [J]. Carcinogenesis, 1998, 19(5):881-888.
[52] Latinwo LM, Ikediobi CO, Singh NP, et al. Comparative studies of in vivo genotoxic effects of cadmium chloride in rat brain, kidney and liver cells [J]. Cell Mol. Biol., 1997,43:203-210.
[53] Valverde M, Fortoul TI, Diaz-Barriga F, et al. Induction of genotoxicity by cadmium chloride inhalation in several organs of CD-I mice [J]. Mutagenesis, 2000, 15:109-114.
[54] Lakin ND, Jackson SP. Regulation of p53 in response to DNA damage [J]. Oncogene, 1999 13;18(53):7644-55.
[55] Taylor WR, Stark GR. Regulation of the G2/M transition by p53 [J]. Oncogene, 2001,20: 1803-1815
[56] Xu B, Kim ST, Lim DS et al. Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation [J]. Mol Cell Biol., 2002, 22(4): 1049-59.
[57] Brown EJ, Baltimore D. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance [J]. Genes Dev. 2003, 17(5):615-28.
[58] Lakin ND, Jackson SP. Regulation of p53 in response to DNA damage [J]. Oncogene. 1999 13;18(53):7644-55.
[59] Cistulli CA, Kaufmann WK. p53-dependent signaling sustains DNA replication and enhances clonogenic survival in 254 nm ultraviolet-irradiated human fibroblasts [J]. Cancer Research, 1998, 58(9): 1993-2002.
[60] Cordeiro-Stone M, Frank A, Bryant M et al. DNA damage responses protect xeroderma pigmentosum variant from UVC-induced clastogenesis [J]. Carcinogenesis, 2002, 23(6):959-965.
[61] Pardee AB. Regulation, restriction, and reminiscences [J]. J Biol Chem., 2002, 277(30):26709-16.
[62] Paulovich AG, Hartwell LH. A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage [J]. Cell. 1995, 82(5):841-7.
[63] Dunphy, W. G. (1994). The decision to enter mitosis [J]. Trends Cell Biol. 4, 202-207.
[64] Mueller, P. R., Coleman, T. R., Kumagai, A et al. Mytl: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15 [J]. Science, 1995,270,86-90.
[65] Fleck, O. and Nielsen, O. DNA repair [J]. J. Cell Sci. 2004, 117: 515-517.
[66] Zhao H, Piwnica-Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1 [J]. Mol Cell Biol. 2001, 21(13):4129-39.
[67] Shiloh Y. Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart [J]. Annu Rev Genet. 1997, 31:635-62.
[68] Banin S, Moyal L, Shieh S et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage [J]. Science. 1998, 281(5383):1674-7.
[69] Gately DP, Hittle JC, Chan GK et al. Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity [J]. Mol Biol Cell. 1998,9(9):2361-74.
[70] Chan DW, Son SC, Block W et al. Purification and characterization of ATM from human placenta. A manganese-dependent, wortmannin-sensitive serine/threonine protein kinase [J]. J Biol Chem. 2000, 275(11):7803-10.
[71] Canman CE, Lim DS, Cimprich KA et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 [J]. Science. 1998, 281(5383):1677-9.
[72] Lim DS, Kim ST, Xu B et al. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway [J]. Nature. 2000, 404(6778):613-7.
[73] Cortez D, Wang Y, Qin J et al. Requirement of ATM-dependent phosphorylation of brcal in the DNA damage response to double-strand breaks [J]. Science. 1999, 286(5442): 1162-6.
[74] Kaufmann WK, Paules RS. DNA damage and cell cycle checkpoints [J]. FASEB Journal, 1996, 10(2):238-247.
[75] Melo J, Toczyski D et al. A unified view of the DNA-damage checkpoint [J]. Curr Opin Cell Biol, 2002, 14(2):237-245.
[76] Osborn AJ, Elledge SJ, Zou L. Checking on the fork: the DNA-replication stress-response pathway [J]. Trends Cell Biol, 2002, 12(11):509-516.
[77] Abraham RT. Cell cycle checkpoint signaling through the ATM and ATR kinases [J]. Genes Dev, 2001, 15(17):2177-2196.
[78] Wang XW, Zhan Q, Coursen JD et al. GADD45 induction of a G2/M cell cycle checkpoint [J]. Proc Natl Acad Sci, 1999, 96(7):3706-3711.
[79] Yang Q, Manicone A, Coursen JD et al. Identification of a Functional Domain in a GADD45-mediated G2/M Checkpoint [J]. J Biol Chem 2000, 275(47): 36892 - 36898.
[80] Zhan Q, Antinore MJ, Wang XW et al. Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45 [J]. Oncogene, 1999, 18(18):2892-2900.
[81] Banin S, Moyal L, Shieh S et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage [J]. Science, 1998, 281(5383): 1674-1677.
[82] Ryan KM, Phillips AC, Vousden KH. Regulation and function of the p53 tumor suppressor protein [J]. Curr Opin Cell Biol, 2001, 13(3):332-337.
[83] Zhang Y, Xiong Y. Ap53 amino-terminal nuclear export signal inhibited by DNA damage-induced phosphorylation [J]. Science, 2001, 292(5523):1910-1915.
[84] Matsuoka M, Igisu H. Cadmium induces phosphorylation of p53 at serine 15 in MCF-7 cells [J]. Biochem Biophys Res Commun, 2001, 282(5): 1120-1125.
[85] Meplan C, Mann K, Hainaut P. Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells [J]. J Biol Chem, 1999, 274(44):31663-31670.
[86] Mukherjee JJ, Gupta SK, Kumar S et al. Effects of cadmium(II) on (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-induced DNA damage response in human fibroblasts and DNA repair: a possible mechanism of cadmium's cogenotoxicity [J]. Chem Res Toxicol, 2004, 17(3):287-293.
[87] Leach SD, Scatena CD, Keefer CJ et al. Negative regulation of Weel expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis [J]. Cancer Res, 1998, 58(15):3231-3236.
[88] Passalaris TM, Benanti JA, Gewin L et al. The G(2) checkpoint is maintained byredundant pathways [J]. Mol Cell Biol, 1999, 19(9):5872-5881.
[89] Deming PB, Cistulli CA, Zhao H et al. The human decatenation checkpoint [J]. Proc Natl Acad Sci, 2001, 98(21): 12044-12049.
[90] Banfalvi G, Littlefield N, Hass B et al. Effect of cadmium on the relationship between replicative and repair DNA synthesis in synchronized CHO cells [J]. Eur J Biochem., 2000, 267(22):6580-6585.
[91] Von Zglinicki T, Edwall C, Ostlund E et al. Very low cadmium concentrations stimulate DNA synthesis and cell growth [J]. J Cell Sci, 1992, 103:1073-1081.
[92] Waalkes MP. Cadmium carcinogenesis [J]. Mutat Res, 2003, 533(1-2): 107-120.
[93] Beyersmann D, Hechtenberg S. Cadmium, gene regulation, and cellular signalling in mammalian cells[J]. Toxicol Appl Pharmacol, 1997, 144(2):247-261.
[94] Nocentini S. Inhibition of DNA replication and repair by cadmium in manmmalian cells. Protective interaction of zinc [J]. Nucleic Acids Research. 1987, 15(10): 4211-4225.
[95] Popenoe EA, Schmaeler MA. Interaction of human DNA polymerase beta with ions of copper, lead, and cadmium [J]. Arch Biochem Biophys., 1979, 196(1): 109-20..
[96] Prasad AS, Oberleas D. Thymidine kinase activity and incorporation of thymidine into DNA in zinc-deficient tissue [J]. J Lab Clin Med., 1974, 83(4):634-9.
[97] Clark AB, Kunkel TA, Cadmium inhibits the functions of eukaryotic MutS complexes [J]. J Biol Chem 2004, 279(52):53903-53906.
[98] Falck J, Mailand N, Syljuasen RG et al. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis [J]. Nature 2001, 410 (6830): 842-847.
[99] Dimri GP, Lee X, Basile G et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo [J]. Proc. Natl Acad. Sci. 1995, 92: 9363 - 9367.
[100] Wang Y, Meng A, Zhou D. Inhibition of phosphatidylinostol 3-kinase uncouples H2O2-induced senescent phenotype and cell cycle arrest in normal human diploid fibroblasts [J]. Exp Cell Res., 2004, 298:188-96.
[101] Marcotte R, Wang E. Replicative senescence revisited [J]. A Biol. Sci. Med. Sci., 2002, 57: B257-B269.
[102] Serrano M, Blasco MA. Putting the stress on senescence [J], Curr. Opin. Cell Biol., 2001, 13:748-753
[103] Serrano M, Blasco MA. Putting the stress on senescence [J], Curr. Opin. Cell Biol., 2001, 13:748-753
[104] Boyer JC, Yamada NA, Roques CN et al. Sequence dependent instability of mononucleotide microsatellites in cultured mismatch repair proficient and deficient mammalian cells [J]. Hum Mol Genet 2002, 11(6):707-713.
[105] Yamada NA, Castro A, Farber RA. Variation in the extent of microsatellite instability in human cell lines with defects in different mismatch repair genes [J]. Mutagenesis, 2003, 18(3):277-282.
[106] Luria SF, Delbruck M. Mutations of bacteria from virus sensitivity to virus resistance[J]. Genetics, 1943, 28:491-511.
[107] Capizzi RL, Jameson JW. A table for the estimation of the spontaneous mutation rate of cells in culture [J]. Mutat Res., 1973, 17(1):147-148.
[108] Yamada NA, Parker JM, Farber RA. Mutation frequency analysis of mononucleotide and dinucleotide repeats after oxidative stress [J]. Environ Mol Mutagen 2003, 42(2):75-84.
[109] Mark J. S and Peggy H. DNA mismatch repair molecular mechanisms and biological function [J]. Annu. Rev. Microbiol., 2003. 57:579-608
[110] Banerjee S, Flores-Rozas H. Cadmium inhibits mismatch repair by blocking the ATPase activity of the MSH2-MSH6 complex [J]. Nucleic Acids Res., 2005, 33 (4): 1410-1419.
[111] Bacon AL, Farrington SM, Dunlop MG. Mutation frequency in coding and non-coding repeat sequences in mismatch repair deficient cells derived from normal human tissue [J]. Oncogene, 2001, 20(51):7464-7471.
[112] Jin YH, Clark AB, Slebos RJ et al. Cadmium is a mutagen that acts by inhibiting mismatch repair [J]. Nat Genet., 2003, 34(3):326-329.
[113] Griffiths K, Morton MS, Denis L. Certain aspects of molecular endocrinology that relate to the influence of dietary factors on the pathogenesis of prostate cancer [J]. Eur Urol, 1999,35:443-55
[114] Tham DM, Gardner CD, Haskel WL. Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence [J]. J Clin Endocrinol Metab, 198, 83: 2223-2235.
[115] Schleicher RL, Lamartiniere CA, Zheng M, et al .The inhibitory effect of genistein on the growth and metastasis of a transplantable rat accessory sex gland carcinoma [J]. Cancer Lett., 1999 ,136(2):195-201.
[116] Zhou JR, Gugger ET, Tanaka T, et al. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice [J].JNutr,1999,129(9): 1628-35.
[117] Suzuki K, Koike H, Matsui H, et al. Genistein, a soy isoflavone. induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3 [J]. Int J Cancer, 2002 ,99(6):846-52.
[118] Kuiper GGJM, Enmark E, Pelto-Huikko M, et al. Cloning of a novel estrogen receptor expressed in rat prostate and ovary [J]. Proc Natl Acad Sci USA, 1996, 93: 5925-5930.
[119] Laura S, Ramon P. PTEN: Life as a Tumor Suppressor Experimental [J]. Cell Resesrch, 2001, 264: 29-41
[120] Koul D , Shen R, Garyali A, et al. MMAC/PTEN tumor suppressor gene regulates vascular endothelial growth factor-mediated angiogenesis in prostate cancer [J]. Int J Oncol, 2002 , 21(3): 469-75
[121] Ming HZ, Jiake X, Peter R, et al. Gene expression of vascular endothelial growth factor in giant cell tumors of bone [J]. Human Pathology, 2000, 31: 804-812
[122] Kazuko S. Synergistic effects of thearubigin and genistein on human prostate tumor cell (PC-3) growth via cell cycle arrest [J]. Cancer Letters, 2000, 151: 103-109
[123] Takashi K, Teruhiro N, Takejiro K. Effect of fiavonoids on cell cycle progression in prostate cancer cells [J]. Cancer Letters, 2002, 176: 17-23
[124] Grunwald V, DeGraffenried L, Russel D, et al. Inhibitors of mTOR Reverse Doxorubicin Resistance Conferred by PTEN Status in Prostate Cancer Cells [J]. Cancer Resesrch, 2002, 62: 6141-6145
[125] Mitchell JH, Duthie SJ, Collins AR. Effects of phytoestrogens on growth and DNA integrity in human prostate tumor cell lines: PC-3 and LNCaP [J]. Nutr Cancer, 2000, 38(2): 223-8
[126] Kazuhiro S, Hidekazu K, Hiroshi M. Genistein, a soy isoflavone,induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3 [J]. Int. J Cancer, 2002, 99: 846-852
[127] Davis J.N, Singh B,Bhuiyan M, et al. Genistein-induced upregulation of p21 WAF1,downregulation of cyclin B, and induction of apoptosis in prostate cancer cells [J]. Nutr. Cancer, 1998, 32: 123-131
[128] Cotroneo MS, Wang W, Eltoum IE, et al. Sex steroid receptor regulation by genistein in the prepubertal rat uterus [J]. Mol. Cell. Endocrinol, 2001, 173: 135-145.
[129] Denis L, Morton MS, Griffiths K. Diet and its preventive role in prostatic disease [J]. Eur Urol, 1999, 35: 377-387
[130] Lamartiniere CA, Cotroneo MS, Fritz WA, et al. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate [J]. J Nutr, 2002, 132(3): 552S-558S
[131] Prins GS, Birch L. Neonatal estrogen exposure up-regulates estrogen receptor expression in the developing and adult rat prostate lobes [J]. Endocrinology, 1997, 138: 1801-1809.
[132] Klein KO. Isoflavones, soy-based infant formulas, and relevance to endocrine function [J]. Nutr. Rev, 1998, 56: 193-204.
[133] Strauss L, Makela S, Joshi S, et al. Genistein exerts estrogen-like effects in male mouse reproductive tract [J]. Mol. Cell. Endocrinol, 1998, 144: 83-93.
[134] Bektic J, Berger AP, Pfeil K, et al. Androgen receptor regulation by physiological concentrations of the isoflavonoid genistein in androgen-dependent LNCaP cells is mediated by estrogen receptor beta [J]. Eur Urol, 2004, 45(2): 245-51
[135] Li P, Yu X, Ge K, et al. Heterogeneous expression and functions of androgen receptor co-factors in primary prostate cancer [J]. Am J Pathol, 2002, 161: 1467-74
[136] Manju S, William WC, Zijie S. Phosphatidylinositol 3-Kinase/Akt Stimulates Androgen Pathway through GSK3P Inhibition and Nuclear P-Catenin Accumulation [J]. The Journal of Biological Chemistry, 2002, 277: 30935-30941.
[137] Pumford SL, Morton MM, Turkes A et al.Determination of the isoflavonoids genistein and daidzein in biological samples by gas chromatography-mass spectrometry [J]. Ann Clin Bio chem, 2002, 39(3):281-292.
[138] Strom S,Yamamura Y, Duphorne CM et al. Phytoestrogen intake and prostate cancer: a case-control study using a new database [J]. Nut Cancer, 1999, 33 (11):20-25.
[139] Kirk P, Patterson RE, Lampe J. Development of a soy food frequency questionnaire to estimate isoflavone consumption in US adults [J]. J Am Diet Assoc, 1999,99:558-563.
[140] Chen Z, Zheng W, Custer LJ et al. Usual dietary consumption of soy foods ant its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai [J]. Nutr Cancer, 199, 33: 82-87.
[141] Wakai K, Egami I, Kato K et al. Dietary intake and sources of isoflavone among Japanese [J]. Nutr Cancer, 1999, 33: 139-145.
[142] Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence [J]. Cancer Cause Control, 1998, 9: 553-557.
[1] Adlercreutz H, Mazur W, Bartels P et al. Phytoestrogens and Prostate Disease [J]. Journal of Nutrition, 2000,130:658S-659S.
[2] Griffiths K, Morton MS, Denis L. Certain aspects of molecular endocrinology that relate to the influence of dietary factors on the pathogenesis of prostate cancer [J]. Eur Urol,1999,35(5-6):443-55.
[3] Strom SS, Yamamura Y, Duphorne CM et al . Phytoestrogen intake and prostate cancer: a case-control study using a new database [J]. Nutr Cancer, 1999,33(1):20-5.
[4] Jacobsen BK, Knutsen SF, Fraser GE. Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study [J]. Cancer Causes Control, 1998,9(6):553-7.
[5] Schleicher RL, Lamartiniere CA, Zheng M et al .The inhibitory effect of genistein on the growth and metastasis of a transplantable rat accessory sex gland carcinoma. Cancer Lett 1999 ,136(2):195-201.
[6] Zhou JR, Gugger ET, Tanaka T et al. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice [J]. J Nutr,1999,129(9):1628-35.
[7] Lamartiniere CA, Cotroneo MS, Fritz WA et al. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate [J]. J Nutr ,2002 ,132(3):552S-558S.
[8] Pollard M, Wolter W. Prevention of spontaneous prostate-related cancer in Lobund-Wistar rats by a soy protein isolate/isoflavone diet [J]. Prostate, 2000,45(2):101-5.
[9] Geller J, Sionit L, Partido C et al. Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture [J] Prostate, 1998,34(2):75-9.
[10] Suzuki K, Koike H, Matsui H et al. Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3 [J]. Int J Cancer, 2002 ,99(6):846-52.
[11] Mitchell JH, Duthie SJ, Collins AR. Effects of phytoestrogens on growth and DNA integrity in human prostate tumor cell lines: PC-3 and LNCaP [J]. Nutr Cancer, 2000,38(2):223-8.
[12] Weber KS, Setchell KD, Stocco DM et al . Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats [J]. J Endocrinol, 2001,170(3):591-9.
[13] Sun XY, Plouzek CA, Henry JP et al. Increased UDP-glucuronosyltransferase activity and decreased prostate specific antigen production by biochanin A in prostate cancer cells [J]. Cancer Res, 1998,58(11):2379-84.
[14] Dalu A, Haskell JF, Coward L, et al. Genistein, a component of soy, inhibits the expression of the EGF and ErbB2/Neu receptors in the rat dorsolateral prostate [J]. Prostate, 1998 ,37(1):36-43.
[15] Peterson G, Barnes S. Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation [J]. Prostate, 1993,22(4):335-45.
[16] Davis JN, Singh B, Bhuiyan M et al. Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells [J]. Nutr Cancer, 1998,32(3):123-31.
[17] Onozawa M, Fukuda K, Ohtani M et al. Effects of soybean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP [J]. Jpn J Clin Oncol ,1998,28(6):360-3.
[18] Shen JC, Klein RD, Wei Q et al. Low-dose genistein induces cyclin-dependent kinase inhibitors and G(1) cell-cycle arrest in human prostate cancer cells [J]. Mol Carcinog, 2000,29(2):92-102.
[20] Kumi-Diaka J, Sanderson NA, Hall A. The mediating role of caspase-3 protease in the intracellular mechanism of genistein-induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP [J]. Biol Cell, 2000,92(8-9):595-604.
[21] Bhatia N, Agarwal R. Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145. cells [J]. Prostate, 2001,46(2):98-107.
[22] Bergan R, Kyle E, Nguyen P, et al. Genistein-stimulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-1-integrin [J]. Clin Exp Metastasis, 1996,14(4):389-98.