IN-VITRO ADRENAL BIOACTIVATION AND EFFECTS ON STEROID-METABOLISM OF DDT, PCBS AND THEIR METABOLITES IN THE GRAY SEAL (HALICHOERUS-GRYPUS)

The irreversible binding of the DDT metabolites op'-DDD hlorophenyl)-2 (4-chlorophenyl)-1,1-dichloroethane] and MeSO2-DDE fonyl-2,2-bis(4-chl orophenyl)-1,1-dichloroethene], as well as their potential to inhibit mitochondrial steroid 11beta-hydroxylation in the gray seal adrenal gl and, was studied. The adrenal bioactivated both o, p'-DDD and MeSO2-DD E in vitro. The irreversible binding of op'-DDD was, however, 17 times higher than that of MeSO2-DDE. In both cases, the enzymes responsible for the activation resided primarily in mitochondria, and inhibitory effects of cytochrome P450 inhibitors (metyrapone and SKF 525A) and NA DPH omission indicated mitochondrial P450 enzymes as responsible for t he bioactivation. Forty-micromolar concentrations of o, p'-DDD and p, p'-DDT rophenyl)-2(4-chlorophenyl)-1,1,1-trichloroethane] inhibited 11 beta-hydroxylation of glucocorticoids (10 muM) by approximately 25%. I n contrast, none of the studied compounds -MeSO2-DDE, p, p'-DDE, some PCBs, and methyl sulfonyl-PCBs (40 muM) - affected the mitochondrial 1 1beta-hydroxylase activity. Bioactivation of environmental pollutants such as DDT and PCB metabolites and inhibition of P450 11beta-hydroxyl ase are discussed as possible reasons for the generation of the adreno cortical hyperplasia observed in Baltic seals.