INCREASE OF CYTOCHROME-P-450 1A AND GLUTATHIONE TRANSFERASE TRANSCRIPTS IN CULTURED-HEPATOCYTES FROM DOGS, MONKEYS, AND HUMANS AFTER CRYOPRESERVATION

The study was designed to investigate the effects of phenobarbital (PB ), 3-methylcholanthrene (3-MC), and oltipraz (OPZ), a synthetic deriva tive of 1,2-dithiole-3-thione, on the levels of cytochrome P450 1A1/2 and gluthathione transferase (GST) mRNAs in both fresh and cryopreserv ed human, monkey, and dog hepatocytes in primary culture. GST alpha mR NAs were demonstrated in liver parenchymal cells from the three specie s: after 4 days of culture, their basal levels were decreased, but wer e strongly higher in PB- and OPZ-treated cells from the three species. In contrast 3-MG was mostly effective on human hepatocytes. The incre ased levels of GST a mRNAs in the presence of PB or OPZ were not obser ved in all cell populations. GST mu mRNAs, which were detected in both dog and monkey hepatocytes, were induced only in the presence of OPZ. GST pi mRNAs were expressed in dog hepatocytes but did not respond to any of the inducers. In all cases, similar effects were observed in f resh and thawed hepatocytes. Similarly, CYP1A1/2 transcripts were indu ced by 3-MG in both fresh and cryopreserved cells from the three speci es but also after OPZ treatment for monkey hepatocytes. These findings demonstrate that enzymes which play a major role in bioactivation/det oxication of xenobiotics remain expressed and inducible in hepatocytes from various species after cryopreservation and thawing.