title: Time- and dose-dependent DNA binding of PAHs derived from diesel particle extracts, benzo[a]pyrene and 5-methychrysene in a human mammary carcinoma cell line (MCF-7).
abstract: Cultures of a human mammary carcinoma cell line (MCF-7) were exposed to the soluble organic fraction of diesel particle emissions, benzo[a]pyrene (B[a]P) and 5-methylchrysene (5-MeCHR) to study time- and dose-related PAH-DNA binding. The concentrations of 14 PAHs in three extracts were analyzed by HPLC and PAH-DNA adducts were measured by (32)P post-labeling assay. Time-dependent DNA adducts formation of 2.5 microM B[a]P was lower than that of 2.5 microM 5-MeCHR. In comparison with B[a]P, 2-fold higher adduct formation by 5-MeCHR was observed at 12 h exposure, after which BPDE adducts decreased and 5-MeCHR continued to form adducts linearly during 48 h exposure. The data for these two PAH compounds demonstrate a large variation in adduct-forming potency, which should be taken into account when estimating DNA adducts formed by mixtures of unknown PAHs. A clear dose-response effect on formation of DNA adducts was obtained for B[a]P and a Standard Reference Material (SRM) of diesel particulate matter. The amount of B[a]P contributed more to total DNA adduct formation by SRM than by three diesel extracts. Thus, no conclusions can be drawn from diesel particle-derived B[a]P as to the adduct-forming potency of other carcinogenic PAHs. There was little change in adduct levels formed by three diesel extracts from 0 to 12 h exposure. Thereafter, the number of adducts formed by RD2 increased more rapidly than those formed by RD1 and EN97. The concentrations of 14 PAHs and adduct levels analyzed at 24 and 48 h did not change in the same proportion between the extracts. Neither could PAH-DNA adduct levels be explained by the sum of strong and weak adduct-forming PAHs analyzed in the extracts. This indicates that other PAHs in the extracts RD1, RD2 and EN97 contributed to adduct formation more than the carcinogenic adduct-forming PAHs analyzed in this study.
authors: FIOH, Topeliuksenkatu 41b, FIN-00250 Helsinki, Finland.
authors: T
authors: T
authors: Kuljukka-Rabb
authors: K
authors: K
authors: Peltonen
authors: S
authors: S
authors: Isotalo
authors: S
authors: S
authors: Mikkonen
authors: L
authors: L
authors: Rantanen
authors: K
authors: K
authors: Savela
mesh_terms: D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D001943:Breast Neoplasms / Q000378:metabolism*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000378:metabolism*; D002911:Chrysenes / Q000378:metabolism* / Q000633:toxicity; D018736:DNA Adducts / Q000032:analysis*; D004273:DNA, Neoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005742:Gasoline / Q000633:toxicity*; D006801:Humans; D012307:Risk Factors; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D002911:Chrysenes; D018736:DNA Adducts; D004273:DNA, Neoplasm; D005742:Gasoline; D001564:Benzo(a)pyrene; C008422:5-methylchrysene