title: Influence of the alkyl substituent on mutagenicity and covalent DNA binding of bay region diol-epoxides of 7-methyl- and 7-ethylbenz(a)anthracene in Salmonella and V79 Chinese hamster cells.
abstract: The anti-isomers of the bay region diol-epoxides of the strong carcinogen 7-methylbenz(a)anthracene and of the weak carcinogen 7-ethylbenz(a)anthracene were investigated for mutagenicity in Salmonella typhimurium (reversion of the his - strains TA98 and TA100 to prototrophy) and V79 Chinese hamster cells (acquisition of resistance to 6-thioguanine and ouabain; formation of micronuclei). In addition, in the V79 cells, the levels of the DNA adducts formed were determined by 32P-postlabeling analysis. In terms of mutations per nmol compound administered, the methyl derivative was four to 10 times more potent, depending on the genetic endpoint, than its ethyl congener. However, when the results were expressed as mutations per adduct, the difference between the two diol-epoxides was small. Therefore, a higher level of DNA modification appears to be the major reason for the stronger mutagenicity of the methyl derivative. However, both diol-epoxides had similar half-lives (about 9 min) in physiological buffer, as determined from the decline in mutagenic activity after preincubation of the test compound. These results suggest that the effect of the 7-alkyl group on the extent of reaction with DNA is more a result of steric factors than of a change in the intrinsic chemical reactivity of the diol-epoxides.
authors.affiliation: Department of Toxicology of the University, Mainz, Federal Republic of Germany.
authors.forename: H
authors.initials: H
authors.lastname: Glatt
authors.forename: R G
authors.initials: RG
authors.lastname: Harvey
authors.forename: D H
authors.initials: DH
authors.lastname: Phillips
authors.forename: A
authors.initials: A
authors.lastname: Hewer
authors.forename: P L
authors.initials: PL
authors.lastname: Grover
mesh_terms: D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D001551:Benz(a)Anthracenes; D002273:Carcinogens; D009153:Mutagens; C054489:7-ethylbenz(a)anthracene; D004247:DNA; C021219:7-methylbenzanthracene