Abstract
The study was designed to investigate the effects of phenobarbital (PB), 3-methylcholanthrene (3-MC), and oltipraz (OPZ), a synthetic derivative of 1,2-dithiole-3-thione, on the levels of cytochrome P450 1A1/2 and gluthathione transferase (GST) mRNAs in both fresh and cryopreserved human, monkey, and dog hepatocytes in primary culture. GST α mRNAs were demonstrated in liver parenchymal cells from the three species: after 4 days of culture, their basal levels were decreased, but were strongly higher in PB- and OPZ-treated cells from the three species. In contrast 3-MC was mostly effective on human hepatocytes. The increased levels of GST α mRNAs in the presence of PB or OPZ were not observed in all cell populations. GST μ mRNAs, which were detected in both dog and monkey hepatocytes, were induced only in the presence of OPZ. GST π mRNAs were expressed in dog hepatocytes but did not respond to any of the inducers. In all cases, similar effects were observed in fresh and thawed hepatocytes. Similarly, CYP1A1/2 transcripts were induced by 3-MC in both fresh and cryopreserved cells from the three species but also after OPZ treatment for monkey hepatocytes. These findings demonstrate that enzymes which play a major role in bioactivation/detoxication of xenobiotics remain expressed and inducible in hepatocytes from various species after cryopreservation and thawing.
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Abbreviations
- GST:
-
glutathione transferase
- CYP:
-
cytochrome P450
- PB:
-
phenobarbital
- 3-MC:
-
3-methylcholanthrene
- OPZ:
-
oltipraz
- DMSO:
-
dimethylsulfoxide
- FCS:
-
fetal calf serum
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de Sousa, G., Langouët, S., Nicolas, F. et al. Increase of cytochrome P-450 1A and glutathione transferase transcripts in cultured hepatocytes from dogs, monkeys, and humans after cryopreservation. Cell Biol Toxicol 12, 351–358 (1996). https://doi.org/10.1007/BF00438170
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DOI: https://doi.org/10.1007/BF00438170