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Abstract The intraperitoneal administration of aromatic hydrocarbons such as 3-methylcholanthrene, β-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, 8-tetrachlorodibenzo-p-dioxin (TCDD) causes induction of a similar magnitude in either responsive or nonresponsive mice of: (a) aryl hydrocarbon (benzoapyrene) hydroxylase activity in liver, bowel, lung, kidney, and skin; (b) 7-ethoxycoumarin O-deethylase activity in liver and kidney; (c) hepatic p-nitroanisole O-demethylase and 3-methyl-4-methylaminoazobenzene Ndemethylase activities; and (d) the new formation of cytochrome P1-450 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/2N, DBA/2J, 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 activities and associated new formation of cytochrome P1-450 and that the defect in these mice is a failure to recognize aromatic hydrocarbons which are less potent inducers. In the nonresponsive inbred strains, perhaps a mutation has occurred which results in production of an inducerbinding receptor having a diminished affinity for aromatic hydrocarbons.
Poland et al. (1974) studied this question.