Tissue-specific induction and inactivation of cytochrome P450 catalysing lauric acid hydroxylation in the sea bass, Dicentrarchus labrax

Microsomal cytochrome P450-dependent lauric acid hydroxylase activities wer e characterized in liver, kidney, and intestinal mucosa of the sea bass (Di centrarchus labrax). Microsomes from these organs generated (omega-1)-hydro xylauric acid and a mixture of positional isomers including (omega)-, (omeg a-2)-, (omega-3)- and (omega-4)-hydroxylauric acids, which were identified by RP-HPLC and GC-MS analysis. Peroxisome proliferators, such as clofibrate and especially di(2-ethylhexyl) phthalate, increased kidney microsomal lau ric acid hydroxylase activities. The synthesis of 11-hydroxylauric acid was enhanced 5.3-fold in kidney microsomes. Liver microsomal lauric acid hydro xylase activities were weakly affected and no significant induction was fou nd in small intestine microsomes from clofibrate or di(2-ethylhexyl) phthal ate-treated fish. The differences in lauric acid metabolisation and the tis sue-specific induction by peroxisome proliferators suggest the involvement of several P450s in this reaction. Incubations of liver and kidney microsom es with lauric acid analogues (11- or 10-dodecynoic acids) resulted in a ti me- and concentration-dependent loss of lauric acid hydroxylase activities. The induction of these activities in fish by phthalates, which are widely- distributed environmental pollutants, may be taken into consideration for t he development of new biomarkers. (C) 1999 Elsevier Science Ltd. All rights reserved.