Metabolism and toxicity of xenobiotics in the adrenal cortex, with particular reference to 7,12-dimethylbenz(a)anthracene.
The adrenal cortex contains high amounts of detoxifying enzymes, as well as generators and protectors of reactive oxygen species. The high content of cytochrome P-450 enzymes in the adrenal cortex together with its remarkable tendency to accumulate hydrophobic substances probably contributes to the extraordinary vulnerability of the gland to a number of xenobiotics. The best studied adrenocorticolytic compounds are the potent carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) and its liver metabolite 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA). Adrenocorticolysis generated by these agents in vivo as well as in vitro demonstrates high regioselective requirements and is strongly influenced by the presence of ACTH, steroids, cytochrome P-450 inhibitors and antioxidants. Furthermore, 7-OHM-12-MBA has been demonstrated to uniquely generate selective and massive oxidation of mitochondrial glutathione in cultured rat adrenal cells. The DMBA-induced adrenocorticolysis is thoroughly discussed in this review with particular emphasis on the metabolism of DMBA and the influence of various effectors. A working hypothesis involving a possible peroxidative mechanism is also presented.
Hallberg
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Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism* / Q000633:toxicity; D000302:Adrenal Cortex / Q000378:metabolism*; D000307:Adrenal Gland Diseases / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D006801:Humans; D015262:Xenobiotics / Q000378:metabolism* / Q000633:toxicity
D015262:Xenobiotics; D015127:9,10-Dimethyl-1,2-benzanthracene