Mutagenic activity of methyl- and fluoro-substituted derivatives of polycyclic aromatic hydrocarbons in a human hepatoma (HepG2) cell-mediated assay.
Several series of methyl- and fluoro-substituted polycyclic aromatic hydrocarbon (PAH) derivatives were tested for mutagenic activity in cell-mediated assays with cells of the human hepatoma cell line, HepG2, as PAH activators. The mutagenic activity of dibenz[a,h]anthracene [DB(a,h)A] increased progressively with the substitution of a methyl group at one or both non-benzo bay-region sites. At a concentration of 0.25 micrograms/ml, the mutation frequencies induced by DB(a,h)A, and 7,14-diMeDB(a,H)A were 1.3, 13.1 and 59.0 6-thioguanine-resistant colonies/10(5) viable V79 cells, respectively. Methyl groups at non-benzo bay-region sites in 3-methylcholanthrene and benzo[e]pyrene had little effect on mutagenic activity at the highest concentration which could be tested (2 micrograms/ml). The presence of a fluorine atom on the bay-region A-ring of 7,12-dimethylbenz[a]anthracene (DMBA) drastically drastically reduced mutagenic activity. At a concentration of 1.0 micrograms/ml, the mutation frequencies induced by DMBA, 1-fluoro-DMBA and 4-fluoro-DMBA were 50.5, 6.8 and 1.6, respectively. On the other hand, the mutation frequency was increased 6-fold when the fluoro substituent was in the 10-position of the D-ring of DMBA. Thus, for the most part, the relative mutagenic activities of these compounds in the HepG2 cell-mediated assay paralleled their skin tumor-initiating activity in SENCAR mice reported earlier (DiGiovanni et al., 1982, 1983a, b). These studies demonstrate the value of the HepG2 cell line as an exogenous, intact human cell activation system in short-term assays designed to evaluate the genotoxic effects of PAHs.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives; D000818:Animals; D001551:Benz(a)Anthracenes; D001580:Benzopyrenes / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental; D009154:Mutation / Q000187:drug effects*; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D006845:Hydrocarbons, Fluorinated; D006846:Hydrocarbons, Halogenated; D015127:9,10-Dimethyl-1,2-benzanthracene; C026487:benzo(e)pyrene; C026486:1,2,5,6-dibenzanthracene