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)
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
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.