Molecular Dosimetry of Endogenous and Exogenous O6-Methyl-dG and N7-Methyl-G Adducts Following Low Dose [D3]-Methylnitrosourea Exposures in Cultured Human Cells

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• 作者：Vyom Sharma ; Leonard B. Collins ; Jean M. Clement ; Zhenfa Zhang ; Jun Nakamura ; James A. Swenberg
• 刊名：Chemical Research in Toxicology
• 出版年：2014
• 出版时间：April 21, 2014
• 年：2014
• 卷：27
• 期：4
• 页码：480-482
• 全文大小：173K
• 年卷期：v.27,no.4(April 21, 2014)
• ISSN：1520-5010

文摘

For DNA-reactive chemicals, a low dose linear assessment of cancer risk is the science policy default. In the present study, we quantitated the endogenous and exogenous N7-methyl-G and O⁶-methyl-dG adducts in human lymphoblastoid cells exposed to low dose [D₃]-methylnitrosourea. Endogenous amounts of both adducts remained nearly constant, while the exogenous adducts showed linear dose-responses. The data show that O⁶-methyl-dG adducts 鈮?.8/10⁸ dG correlated with published studies that demonstrated significant increases of mutations under these conditions. The combined results do not support linear extrapolations to zero when data are available for science-based regulations.