Adrenocorticolytic DDT-metabolites: studies in mink, Mustela vison and otter, Lutra lutra

Abstract

: The irreversible binding and toxicity of the DDT metabolites p,p'-DDD and o,p-DDD in the adrenal cortex of female mink Mustela vison were studied. Histological examination of adrenals from mink given a single i.p. injection of p,p'-DDD or o,p'-DDD (125 mg per kg body weight) showed vacuolation, necrosis and focal bleedings in the zonae fasciculata and reticularis. Autoradiograms of solvent-extracted tissue sections of minks given a single i.v. injection of p,p'-[(14)C]DDD (0.7 mg per kg body weight) revealed a high level of irreversibly bound radio-activity in the adrenal cortex. Microautoradiography showed that the irreversibly bound radio-activity was confined to the zonae fasciculata and reticularis. Incubation of p,p'-[(14)C]DDD and o,p'-[(14)C]DDD with mink or otter, Lutra lutra, adrenal homogenate (300 x g supernatant) resulted in an irreversible binding of radioactivity to protein from both species. The irreversible protein binding of the DDD isomers in mink and otter was decreased by addition of the cytochrome P450 inhibitors metyrapone and carbon monoxide, indicating a cytochrome P450 dependent metabolic activation. In contrast, 3-methylsulfonyl-[(14)C]DDE, a potent adrenocortical toxicant in mice, does not appear to be metabolized to a reactive metabolite in the adrenal cortex of mink or otter. In conclusion, both p,p'-DDD and o,p'-DDD are toxic to the mink adrenal zona fasciculata and reticularis following activation in situ to reactive, tissue-binding metabolites. The results suggest that p,p'-DDD and o,p'-DDD are adrenocortical toxicants also in otter. The involvement of environmental pollutants in the generation of the adrenocortical hyperplasia observed among Baltic seals is discussed.