NADPH-, NADH- and cumene hydroperoxide-dependent metabolism of benzo[a]pyrene by pyloric caeca microsomes of the sea star Asterias rubens L. (Echinodermata: Asteroidea).
1. Benzo[a]pyrene (BaP) metabolism was studied in microsomes of the pyloric caeca (main digestive tissue and site of P450) of the echinoderm sea star (starfish) Asterias rubens. 2. NADPH-dependent metabolism of BaP produced phenols (36% of total metabolism), quinones (19%), dihydrodiols (25%) and putative protein adducts (20%). 3. NADH-dependent rates of BaP metabolism were approximately twice those found for NADPH-dependent metabolism, and metabolite formation was shifted towards dihydrodiols and quinones. 4. Cumene hydroperoxide (CHP)-dependent rates of BaP metabolism were also higher than NADPH-dependent rates by a factor of six for quinone and putative protein adduct production, and by a factor of four for phenol and dihydrodiol production. 5. Microsomal rates of BaP metabolism in BaP-exposed sea stars appeared to be elevated more in the case of NADPH-dependent than for CHP-dependent metabolism (respectively, increases of 130 and 41%), indicating the induction of forms of P450 preferentially catalysing NADPH-dependent metabolism. 6. 1,1,1-Trichloropropene-2,3-oxide (TCPO) inhibited dihydrodiol formation from both NADPH- and CHP-dependent BaP metabolism, indicating the involvement of epoxide hydratase in BaP metabolism. 7. Incubations of pyloric caeca microsomes with BaP and a superoxide anion radical-generating system (xanthine/xanthine oxidase) produced putative protein adducts but no free metabolites.
den Besten
P J
PJ
NERC Plymouth Marine Laboratory, Citadel Hill, UK.
Lemaire
P
P
Livingstone
D R
DR
D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology*; D009249:NADP / Q000494:pharmacology*; D010636:Phenols / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011708:Pylorus / Q000648:ultrastructure; D011809:Quinones / Q000378:metabolism; D013215:Starfish / Q000378:metabolism*; D014239:Trichloroepoxypropane / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D001555:Benzene Derivatives; D010636:Phenols; D011506:Proteins; D011809:Quinones; D014970:Xanthines; D009243:NAD; D019820:Xanthine; D014239:Trichloroepoxypropane; D001564:Benzo(a)pyrene; D009249:NADP; D014969:Xanthine Oxidase; D004851:Epoxide Hydrolases; C007164:cumene hydroperoxide