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Human Lymphoblast Mutagens in Urban Airborne Particles
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文摘
Whileit is known that urban airborne particles typicallycontain trace levels of bacterial mutagens and rodentcarcinogens, little work has been done to identifychemicalsin such particles that can genetically alter human cells.In this paper, we describe the analysis of an organicextractof a Washington, DC, airborne particle sample (SRM 1649)for human cell mutagens. Due to the chemicalcomplexity of the extract, a bioassay-directedfractionationmethod was used to separate mutagenic constituentsinto chemically simplified fractions. Mutagenicitytestingwas done using the h1A1v2 cell line, a line of humanB-lymphoblastoid cells that have been engineered to overexpress the human cytochrome P4501A1. Chemicalanalysis of mutagenic fractions was accomplished usingGC-MS and HPLC-UV techniques. Our results indicate that~20% of the total mutagenicity the extract wasaccounted for in two fourth-order fractions that contained~3% of the total extract mass. These fractionswerecomposed largely of polycyclic aromatic hydrocarbons(PAH).A total of 13 PAH were identified that accounted for~15%of the mutagenicity of the extract. Of these, themostimportant mutagens were cyclopenta[cd]pyrene,benzo[a]pyrene, and benzo[b]fluoranthene, accounting for~7, ~4,and ~2%, respectively, of the extract mutagenicity.Naphtho[2,1-a]pyrene (N[2,1-a]P) andnaphtho[2,3-a]pyrene (N[2,3-a]P), two previously unknown potent humanlymphoblastmutagens, were also identified in the sample.N[2,1-a]P accounted for ~3% of the extract mutagenicity;N[2,3-a]P, which was present at relatively low levels,accountedfor <1% of the extract mutagenicity. The remainderofthe mutagenicity was found in fractions that containedmorepolar compounds. One of these polar fractionscontainedmany different classes of oxygenated polycyclic aromaticcompounds (oxy-PAH) including ketones, quinones, coumarins, and carboxylic acid anhydrides; however, of themutagenic oxy-PAH identified, only the ketone6H-benzo[cd]pyren-6-one (~0.5%) was found to account for asignificantportion of the total mutagenicity of the extract.Nitro-PAH, many of which are potent bacterial mutagens, did notcontribute significantly to the mutagenicity of thissamplebecause they were present at low concentrations andbecause they are not particularly mutagenic in h1A1v2cells.

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