In vitro adrenal bioactivation and effects on steroid metabolism of DDT, PCBs and their metabolites in the gray seal (Halichoerus grypus)
- Swedish Univ. of Agricultural Sciences, Uppsala (Sweden). Dept. of Pharmacology and Toxicology
The irreversible binding of the DDT metabolites o,p[prime]-DDD [2-(2-chlorophenyl)-2(4-chlorophenyl)-1,1-dichloroethane] and MeSO[sub 2]-DDE [3-methylsulfonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene], as well as their potential to inhibit mitochondrial steroid 11[beta]-hydroxylation in the gray seal adrenal gland, was studied. The adrenal bioactivated both o,p[prime]-DDD and MeSO[sub 2[minus]] DDE is vitro. The irreversible binding of o,p[prime]-DDD was, however, 17 times higher than that of MeSO[sub 2]-DDE. In both cases, the enzymes responsible for the activation resided primarily in mitochondria, and inhibitory effects of cytochrome P450 inhibitors (metyrapone and SKF 525 A) and NADPH omission indicated mitochondrial P450 enzymes are responsible for the bioactivation. Forty-micromolar concentrations of o,p[prime]-DDD and p,p[prime]-DDT [2-(4-chlorophenyl)-2(4-chlorophenyl)-1,1,1-trichloroethane] inhibited 11[beta]-hydroxylation of glucocorticoids (10 [mu]M) by approximately 25%. In contrast, none of the studied compounds-MeSO[sub 2]-DDE, p,p[prime]-DDE, some PCBs, and methylsulfonyl-PCBs (40 [mu]M)--affected the mitochondrial 11[beta]-hydroxylase activity. Bioactivation of environmental pollutants such as DDT and PCB metabolites and inhibition of P450 11[beta]-hydroxylase are discussed as possible reasons for the generation of the adrenocortical hyperplasia observed in Baltic seals.
- OSTI ID:
- 7016139
- Journal Information:
- Environmental Toxicology and Chemistry; (United States), Vol. 13:6; ISSN 0730-7268
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ADRENAL GLANDS
BIOLOGICAL FUNCTIONS
DDT
METABOLISM
PINNIPEDS
SENSITIVITY
POLYCHLORINATED BIPHENYLS
WATER POLLUTION
ANIMALS
AQUATIC ORGANISMS
AROMATICS
BODY
CHLORINATED AROMATIC HYDROCARBONS
ENDOCRINE GLANDS
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
INSECTICIDES
MAMMALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PESTICIDES
POLLUTION
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology