TIME-COURSE AND DOSE-RESPONSE OF THE APPARENT INDUCTION OF THE CYTOCHROME-P450 MONOOXYGENASE SYSTEM OF PYLORIC CECA MICROSOMES OF THE FEMALE SEA STAR ASTERIAS-RUBENS L BY BENZO[A]PYRENE AND POLYCHLORINATED-BIPHENYLS

A study was made on the time-course of putative monooxygenase (MO) induction and the dose-response relationships for the effects of 3,3',4,4',5-pentachlorobiphenyl (IUPAC congener 126), 2,3',4,4',5-pentachlorobiphenyl (congener 118), 2,2',4,4',5,5'-hexachlorobiphenyl (congener 153) and benzo[a]pyrene (BaP) on MO-system activities in female sea stars Asterias rubens L. Sea stars received a single injection of PCB or BaP at different concentrations. Cytochrome P450 concentration and activities of NADPH-cytochrome c(P450) reductase, BaP hydroxylase (BPH) and pregnenolone hydroxylase were determined in microsomal fractions of the pyloric caeca. Apparent induction of BPH activity by PCB was observed only with CB-126 (3-methylcholanthrene (3-MC)-type inducer) at 10 mumol/kg. BPH activity was not affected by CB-153 (phenobarbital-type inducer) or CB-118 (mixed-type inducer). BaP (3-MC-type inducer) elicited a clear dose-dependent BPH induction in the range 10-160 mumol/kg. The maximum observed increase in BPH activity was about 350%. In time-course studies with CB-126 and BaP, highest BPH activities were found 3-4 days after injection. HPLC analysis of microsomal BaP metabolites revealed that the elevated metabolism was shifted towards phenol production. PCB or BaP had no effect on the level of cytochrome P450 or the NADPH-cytochrome c reductase activity. All three PCBs and BaP inhibited pregnenolone hydroxylase activity, but no dose-response relationships were found. Overall the results suggest that the echinoderm MO system is inducible in response to exposure to cytochrome P450 1A-type inducers. However, the mechanism of induction remains unclear.