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

Extremely low stores of vitamin A have been reported in fish and birds inhabiting regions contaminated by coplanar polychlorinated biphenyls (PCBs) and other organochlorines, suggesting many possible effects on retinoid biochemical pathways. Metabolic imbalances associated with biologically active retinoids (e.g., retinoic acid) could be associated with teratogenesis, edema, growth inhibition, reproductive impairment, immunosuppression, and susceptibility to cancer Sexually mature brook trout were injected intraperitoneally 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 microsomes. To our knowledge, retinoic acid conjugation by UDP-glucuronyltransferase is described here for the first time in fish. A substantial rare of glucuronidation was detected in the microsomes from control brook trout, which tended to increase over die dose range of TCBP. Glucuronidation was significantly greater in fish receiving the 10 mu g/g body weight dose level. Metabolism through the cytochrome P450 system was also dose-dependent, resulting in significantly dose level. In contrast, subsequent oxidation to 4-oxo-retinoic acid was greater production of 4-hydroxyretinoic acid at the 10 mu g/g greatest at the 1 mu g/g dose level and did not increase further at higher doses. Liver stores of dehydroretinyl palmitrate/oleate were significantly decreased at the 5 and 10 mu g/g dose levels.