title: Interaction of tributyltin with hepatic cytochrome P450 and uridine diphosphate-glucuronosyl transferase systems of fish: in vitro studies.
abstract: 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 (BaP) metabolism and in terms of glucuronidation of testosterone and 17beta-estradiol, respectively. Ethoxyresorufin O-deethylase and BaP 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 microM TBT for EROD and 250-500 microM TBT for BPH). Hydroxylated metabolites of BaP (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 microM TBT, whereas the formation of other metabolites was less affected. This may alter BaP 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 microM), with no effect on the glucuronidation of estradiol.
authors.affiliation: Environmental Chemistry Department IIQAB-CSIC-, C/Jordi Girona, 18, 08034 Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Morcillo
authors.forename: Gemma
authors.initials: G
authors.lastname: Janer
authors.forename: Sean C M
authors.initials: SC
authors.lastname: O'Hara
authors.forename: David R
authors.initials: DR
authors.lastname: Livingstone
authors.forename: Cinta
authors.initials: C
authors.lastname: Porte
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D005432:Flounder / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology; D023701:Smegmamorpha / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014530:Uridine Diphosphate / Q000494:pharmacology*
chemical_list: D014220:Trialkyltin Compounds; D013739:Testosterone; C011559:tributyltin; D014530:Uridine Diphosphate; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase