Abstract
The mixed-function oxidases1, which contain different forms of cytochrome P450, are the critical enzymes which metabolize a wide variety of drugs, carcinogens and environmental chemicals, as well as steroids and other endogenous metabolites2. The metabolism of these chemicals may result either in their detoxification or in their conversion to toxic, mutagenic and carcinogenic metabolites. Modulation of the mixed-function oxidase, aryl hydrocarbon hydroxylase (AHH), by either inhibitors or inducers strongly affects carcinogenesis induced by polycyclic hydrocarbons3,4. We reported earlier that 7,8-benzoflavone is a potent inhibitor of the form of AHH that is induced by polycyclic hydrocarbons but either weakly inhibits or stimulates the form of AHH derived from the livers of phenobarbital-treated or untreated rats5,6. We now report that the pterocarpan (−)maackiain acetate exhibits unique specificity that is the reverse of 7,8-benzoflavone, that is, it has strong inhibitory activity towards the form of AHH found in human liver or in untreated or phenobarbital-treated rats and weak inhibitory or stimulatory activity towards the AHH induced by polycyclic hydrocarbons in rat tissues or by cigarette smoking in human placenta. Thus, we conclude that (−)maackiain acetate and 7,8-benzoflavone inhibit different forms of AHH.
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Gelboin, H., West, D., Gozukara, E. et al. (−)Maackiain acetate specifically inhibits different forms of aryl hydrocarbon hydroxylase in rat and man. Nature 291, 659–661 (1981). https://doi.org/10.1038/291659a0
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DOI: https://doi.org/10.1038/291659a0
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