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Interaction of tributyltin with hepatic cytochrome P450 and uridine diphosphate‐glucuronosyl transferase systems of fish: In vitro studies
Author(s) -
Morcillo Yolanda,
Janer Gemma,
O'Hara Sean C.M.,
Livingstone David R.,
Porte Cinta
Publication year - 2004
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1897/034-262
Subject(s) - tributyltin , chemistry , glucuronidation , uridine diphosphate , microsome , uridine , glucuronosyltransferase , cytochrome p450 , pyrene , biochemistry , flounder , platichthys , metabolism , enzyme , environmental chemistry , biology , fish <actinopterygii> , fishery , rna , organic chemistry , gene
Hepatic microsomes of red mullet ( Mullus barbatus ) and flounder (Platichthys flesus) were preincubated in the presence of a concentration range of the antifouling agent tributyltin (TBT) chloride, and the interactions of TBT with cytochrome P450 and uridine diphosphate—glucuronyl transferase systems were investigated. The enzyme systems were examined in terms of cytochrome P4501A (CYP1A)‐catalyzed 7‐ethoxyresorufin O ‐deethylase (EROD) activity and benzo[ a ]pyrene (B a P) metabolism and in terms of glucuronidation of testosterone and 17β‐estradiol, respectively. Ethoxyresorufin O ‐deethylase and B a P hydroxylase (BPH) activities of both fish species were progressively inhibited by increasing concentrations of TBT, and the effects were more pronounced for EROD than for BPH (maximal inhibition at 100 μM TBT for EROD and 250–500 μM TBT for BPH). Hydroxylated metabolites of B a P (3‐hydroxy‐, 7,8‐dihydrodiol, and 9,10‐dihydrodiol), representing 95% of the total metabolites formed, were reduced up to 75 % in the presence of 100 to 500 μM TBT, whereas the formation of other metabolites was less affected. This may alter B a P toxicity and carcinogenicity. Overall, the results were consistent with a specific inhibitory effect of TBT on CYP1A in the two fish species. Additionally, the conjugation of testosterone was significantly inhibited (20%) at low TBT doses (5 μM), with no effect on the glucuronidation of estradiol.