DECREASED RESPONSIVENESS OF THE HEPATIC CYTOCHROME-P450 1A1 SYSTEM IN RAINBOW-TROUT (ONCORHYNCHUS-MYKISS) AFTER PROLONGED EXPOSURE TO PCB

In the present study juvenile rainbow trout (Oncorhynchus mykiss) were treated with a single intraperitoneal (i.p.) injection of either carrier vehicle, 3-methylcholanthrene (3-MC) or a commercial PCB mixture (Clophen A50) in a long-term laboratory experiment. The response of the hepatic cytochrome P450 (P450 or CYP) system, measured as CYP1A1 mRNA content, CYP1A1 protein content, ethoxyresorufin-O-deethylase (EROD) activity and total P450 content was monitored over a 20-week time period. In 3-MC-treated fish, the highest degree of CYP1A1 induction was seen after 5 days for mRNA, and after 5-15 days for protein content and EROD activity. After 5 weeks, all parameters were indistinguishable from the corresponding control levels in 3-MC-treated fish. In PCB-treated fish, on the other hand, the CYP1A1 induction was somewhat delayed and it continued to increase at all levels during the whole experimental period. An additional injection of either carrier vehicle, 3-MC or PCB was given 5 and 15 weeks following the first injection of 3-MC and PCB. 3-MC-treated fish showed induced CYP1A1 levels after a second 3-MC injection at both 5 and 15 weeks. PCB-treated fish responded to a 3-MC injection by induced CYP1A1 levels only after 5 weeks. After 15 weeks, the PCB-treated fish were unresponsive to 3-MC treatment and a second PCB injection instead caused a significant decrease in CYP1A1 expression compared to carrier vehicle-injected fish. The present study demonstrates that prolonged exposure to PCB may impair the inducibility of the CYP1A1 system in rainbow trout liver.