Genetic differences in the induction of aryl hydrocarbon hydroxylase and benzo(a)pyrene carcinogenesis in C3H/He and DBA/2 strains of mice.
The effects of 3-methylcholanthrene and 5,6- and 7,8-benzoflavones on aryl hydrocarbon (benzo[a]pyrene) hydroxylase in the liver, small intestine, lung, and skin tissues from C3H/He and DBA/2 strains of mice under the controlled lighting conditions were examined. Apparent differences were observed in the inducibility of the hepatic enzyme by the inducers between the two strains of mice, showing that the enzyme in the C3H/He mice is inducible but not in the DBA/2 mice. Comparison of the results on the enzyme induction by 3-methylcholanthrene in the liver among the parent, intercrossed, and backcrossed mice suggested that the inducibility may be inherited as a single autosomal dominant trait. However, different genetic responses to 3-methylcholanthrene and benzoflavones in the enzyme of small intestine might be considered, because a discrepancy in the inducibility of the enzyme between the liver and the small intestine from the identical mice was demonstrated when the progeny of F2 and (DBA/2 times F1) backcross were used. On the other hand, no apparent difference was found in the inducibility of the enzyme in the lung and skin between the C3H/He and the DBA/2 mice. It is assumed that the genetic regulation of the induction of aryl hydrocarbon hydroxylase was separately controlled in the respective tissues from the identical mice. By the repeated topical applications of benzo[a]pyrene, the incidence of skin cancer was higher in the DBA/2 mice than in the C3H/He mice. The relationship between the induction of aryl hydrocarbon hydroxylase and carcinogenicity in the skin is briefly discussed.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis; D001580:Benzopyrenes; D004790:Enzyme Induction; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*
D001580:Benzopyrenes; D005419:Flavonoids; D008748:Methylcholanthrene; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases