title: Murine susceptibility to two-stage skin carcinogenesis is influenced by the agent used for promotion.
abstract: Several approaches were employed to investigate whether murine stock and strain differences in susceptibility to two-stage skin carcinogenesis are due to differences in the metabolism of the initiating aromatic hydrocarbons, or the consequences of the agents used for promotion. A cell-mediated mutagenesis assay was used to quantitatively compare the abilities of cultured newborn SENCAR, DBA/2, C57BL/6 and BALB/c keratinocytes to metabolize dimethylbenz[a]anthracene (DMBA) to mutagenic and cytotoxic metabolites. At equivalent concentrations of DMBA, throughout a 25-fold range in promutagen concentration, C57BL/6, BALB/c and SENCAR keratinocyte-dependent mutant frequencies were very similar and approximately twice DBA/2 keratinocyte-dependent mutant frequencies. In in vivo tumor studies, C57BL/6 mice were more sensitive than SENCAR mice to complete skin carcinogenesis protocols employing repetitive weekly treatments with DMBA and benzo[a]pyrene (BP). At equivalent concentrations of either DMBA or BP, C57BL/6 mice developed carcinomas sooner, and had a greater number of carcinomas per animal. SENCAR mice were very sensitive to two-stage skin carcinogenesis protocols employing BP and DMBA as initiators and benzoyl peroxide and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoters. C57BL/6 mice were relatively refractory to TPA promotion but sensitive to promotion with benzoyl peroxide. These findings suggest that murine stock and strain-dependent differences in sensitivity to two-stage skin carcinogenesis may not be due to major differences in the metabolism of the initiating hydrocarbons, but are partially the consequences of the agents used for promotion.
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D008168:Lung; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D012867:Skin / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate
chemical_list: D001580:Benzopyrenes; D002273:Carcinogens; D009153:Mutagens; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate