RETINOIC ACID HYDROXYLATION IN RAINBOW-TROUT (ONCORHYNCHUS-MYKISS) AND THE EFFECT OF A COPLANAR PCB, 3,3',4,4'-TETRACHLOROBIPHENYL

When liver microsomes of rainbow trout (Oncorhynchus mykiss) were incu bated with [C-14]-labeled retinoic acid plus NADPH, high performance l iquid chromatography revealed the presence of radioactive peaks having elution times identical to those of 4-hydroxy- and 4-oxoretinoic acid . In the absence of NADPH, the radioactive peaks were not detected whi ch is consistent with cytochrome P450-dependent 4-hydroxylation. In tr out injected intraperitoneally with 5 mu g/g of 3,3',4,4'-tetrachlorob iphenyl (TCB) and sacrificed 56 days later, the hydroxylation rate was higher (P < 0.0005) compared with control trout. No difference was ob served between TCB-treated and control groups 7 days after injection. In contrast, cytochrome P4501-dependent ethoxyresorufin-O-deethylase a ctivity was significantly higher in the TCB-treated group, both at 7 a nd 56 days. Liver retinoid stores were not affected by TCB treatment. These results clearly demonstrate that fish metabolize retinoic acid t hrough a hydroxylation step which can be accelerated by a cytochrome P 4501-inducing coplanar PCB. Given the pronounced biological activity o f retinoic acid and closely related retinoids, increased retinoic acid metabolism could explain some of the effects of PCBs in fish.