Genetic Expression of Aryl Hydrocarbon Hydroxylase Activity INDUCTION OF MONOOXYGENASE ACTIVITIES AND CYTOCHROME PI-450 FORMATION BY 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN IN MICE GENETICALLY “NONRESPONSIVE” TO OTHER AROMATIC HYDROCARBONS*

The intraperitoneal administration of aromatic hydrocarbons such as 3-methylcholanthrene, @-naphthoflavone, or naphthacene induces several monooxygenase activities and the new formation of a spectrally distinct CO-binding cytochrome in genetically “responsive” inbred mouse strains, but these compounds, even when administered chronically at high doses, fail to induce these changes in genetically “nonresponsive” inbred strains. On the contrary, administration of 2,3,7, B-tetrachlorodibenzo-p-dioxin (TCDD) causes induction of a similar magnitude in either “responsive” or “nonresponsive” mice of: (a) aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity in liver, bowel, lung, kidney, and skin; (b) 7-ethoxycoumarin 0-deethylase activity in liver and kidney; (c) hepatic p-nitroanisole Odemethylase and 3-methyl-4-methylaminoazobenzene Ndemethylase activities; and (d) the new formation of cytochrome PI-450 in liver, bowel, lung, kidney, and skin. Application of TCDD to the skin of either “responsive” or “nonresponsive” mice induces aryl hydrocarbon hydroxylase activity more than 6-fold in the skin and also in the liver. The inbred mice used in this study include the “responsive” C57BL/6N, C57BL/6J, C3H/HeN, BALB/cAnN, and CBA/ HN strains and the “nonresponsive” DBA/ZN, DBA/ZJ, AKR/N, NZW/BLN, and NZB/BLN strains. These data demonstrate that genetically “nonresponsive” mice have the structural and regulatory genes necessary for expression of these inducible microsomal monooxygenase