PICROTOXIN IS A CYP1A1 INDUCER IN RAINBOW-TROUT HEPATOCYTES

Picrotoxin is a CYP2B inducer in mammals (1). However, in primary cult ures of rainbow trout hepatocytes we showed CYP1A1 gene expression to be strongly induced as characterized by 7-ethoxyresorufin-O-deethylase activity, immunoblots of CYP1A1 protein, and Northern blots of CYP1A1 mRNA. Induction of CYP1A1 in these cells appeared to be via the aroma tic hydrocarbon (Ah) receptor as indicated by increased levels of Ah r eceptor in the nuclear extracts of picrotoxin treated cells. Picrotoxi n induction of CYP1A1 was blocked by actinomycin D. Superinduction of CYP1A1 mRNA occurred in cells treated with cycloheximide. Coincubation of hepatocytes with picrotoxin and a saturating concentration of 2,3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in synergistic increas es in CYP1A1 gene expression. These results suggest that picrotoxin in duction of CYP1A1 is regulated at the level of transcription and may i nvolve an alternative mechanism(s) to that of TCDD. (C) 1995 Academic Press, Inc.