Interference of benzo[a]pyrene with cytochrome P-450-mediated steroid metabolism in pyloric caeca microsomes of the sea star Asterias rubens L.

Abstract

1. 1. The effects of benzo[a]pyrene (BaP) on the metabolism of progesterone and pregnenolone, and the effects of steroids on BaP metabolism were examined in pyloric caeca microsomes of female Asterias rubens. 2. 2. The patterns of metabolism of progesterone and pregnenolone in microsomes were similar to those found in previous studies for homogenates and tissue incubations of pyloric caeca. 3. 3. BaP reduced the rate of hydroxylation of progesterone and pregnenolone, but had no effect on metabolite formation by non-cytochrome P-450-catalysed reactions. 4. 4. Microsomal BaP hydroxylase activity was reduced by the presence of progesterone, but pregnenolone and testosterone had no such effect. 5. 5. The reductions in steroid or BaP metabolism were progressive with increasing ratios of the concentration of the interfering compound to that of the assay substrate and were maximally 50% or less at ratios of × 100. 6. 6. It is concluded that isoenzymic forms of cytochrome P-450 are present, with preferences towards either steroid or BaP metabolism. The implications of the results for the in vivo situation are discussed.