The importance of the "bay region" diol-epoxide in 7,12-dimethylbenz[a]anthracene skin tumor initiation and mutagenesis.
The skin tumor-initiating and V79 mutagenic activities of various derivatives of 7,12-dimethylbenz[a]anthracene (DMBA) were investigated to determine what possible cellular metabolite(s) may be responsible for its carcinogenicity and/or mutagenicity. 1-,2-,3-,4- and 5-hydroxyDMBA were found to be essentially inactive as skin tumor initiators whereas 9- and 10-hydroxyDMBA had weak activity. The (+/-)-trans DMBA 8,9- and 5,6-dihydrodiols were also essentially inactive as skin tumor initiators and (+/-)-DMBA 8beta,9alpha-diol-10alpha-11alpha-epoxide had weak skin tumor initiating activity. All of the above tested derivatives of DMBA were essentially inactive as mutagens in the cell-mediated or direct V79 mutagenesis systems. A methyl or fluoro addition to the 1, 2 or 5 positions almost completely blocked the skin tumor initiating and V79 mutagenic activities of DMBA, whereas a fluoro addition to position 11 did not. From our data we suggest that a 'bay region' diol-epoxide may be important in DMBA carcinogenicity and mutagenicity.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001551:Benz(a)Anthracenes / Q000031:analogs & derivatives; D002273:Carcinogens; D004353:Drug Evaluation, Preclinical; D005260:Female; D006018:Glycols / Q000494:pharmacology; D051379:Mice; D009153:Mutagens; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010212:Papilloma / Q000139:chemically induced*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D006018:Glycols; D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene