Dose-dependent stimulation of hepatic retinoic acid hydroxylation/oxidation and glucuronidation in brook trout, Salvelinus fontinalis, after exposureto 3,3 ',4,4 '-tetrachlorobiphenyl

Extremely low stores of vitamin A have been reported in fish and birds inha biting regions contaminated by coplanar polychlorinated biphenyls (PCBs) an d other organochlorines, suggesting many possible effects on retinoid bioch emical pathways. Metabolic imbalances associated with biologically active r etinoids (e.g., retinoic acid) could be associated with teratogenesis, edem a, growth inhibition, reproductive impairment, immunosuppression, and susce ptibility to cancer Sexually mature brook trout were injected intraperitone ally with the coplanar PCB 3,3',4,4'-tetrachlorobiphenyl (TCBP) and again 4 weeks Inter. At 8 weeks, retinoic acid metabolism was measured in liver mi crosomes. To our knowledge, retinoic acid conjugation by UDP-glucuronyltran sferase is described here for the first time in fish. A substantial rare of glucuronidation was detected in the microsomes from control brook trout, w hich tended to increase over die dose range of TCBP. Glucuronidation was si gnificantly greater in fish receiving the 10 mu g/g body weight dose level. Metabolism through the cytochrome P450 system was also dose-dependent, res ulting in significantly dose level. In contrast, subsequent oxidation to 4- oxo-retinoic acid was greater production of 4-hydroxyretinoic acid at the 1 0 mu g/g greatest at the 1 mu g/g dose level and did not increase further a t higher doses. Liver stores of dehydroretinyl palmitrate/oleate were signi ficantly decreased at the 5 and 10 mu g/g dose levels.