NADPH-DEPENDNENT, NADH-DEPENDENT AND CUMENE HYDROPEROXIDE-DEPENDENT METABOLISM OF BENZO[A]PYRENE BY PYLORIC CECA MICROSOMES OF THE SEA-STAR, ASTERIAS-RUBENS L (ECHINODERMATA, ASTEROIDEA)

Citation
Pj. Denbesten et al., NADPH-DEPENDNENT, NADH-DEPENDENT AND CUMENE HYDROPEROXIDE-DEPENDENT METABOLISM OF BENZO[A]PYRENE BY PYLORIC CECA MICROSOMES OF THE SEA-STAR, ASTERIAS-RUBENS L (ECHINODERMATA, ASTEROIDEA), Xenobiotica, 24(10), 1994, pp. 989-1001
Citations number
41
Categorie Soggetti
Pharmacology & Pharmacy
Journal title
ISSN journal
00498254
Volume
24
Issue
10
Year of publication
1994
Pages
989 - 1001
Database
ISI
SICI code
0049-8254(1994)24:10<989:NNACHM>2.0.ZU;2-N
Abstract
1. Benzo[a]pyrene (BaP) metabolism was studied in microsomes of the py loric 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%), dihyd rodiols (25%) and putative protein adducts (20%). 3. NADH-dependent ra tes of BaP metabolism were approximately twice those found for NADPH-d ependent metabolism, and metabolite formation was shifted towards dihy drodiols and quinones. 4. Cumene hydroperoxide (CHP)-dependent rates o f BaP metabolism were also higher than NADPH-dependent rates by a fact or of six for quinone and putative protein adduct production, and by a factor of four for phenol and dihydrodiol production. 5. Microsomal r ates of BaP metabolism in BaP-exposed sea stars appeared to be elevate d more in the case of NADPH-dependent than for CHP-dependent metabolis m (respectively, increases of 130 and 41%), indicating the induction o f forms of P450 preferentially catalysing NADPH-dependent metabolism. 6. 1,1,1-Trichloropropene-2,3-oxide (TCPO) inhibited dihydrodiol forma tion 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-gene rating system (xanthine/xanthine oxidase) produced putative protein ad ducts but no free metabolites.