Carcinogenesis Advance Access published online on October 21, 2004
Carcinogenesis, doi:10.1093/carcin/bgh316
© 2004 by Oxford University Press
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1 INSERM U620, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, 35043 Rennes, France
* To whom correspondence should be addressed. Numerous chemical compounds are cytotoxic or carcinogenic for human beings and attention is now focusing on preventative strategies. One agent, oltipraz (OPZ), regarded as one of the most promising chemoprotector, has been shown to be a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxins. However, little is known about its effects on global gene expression in human cells. Thus, we used microarrays membranes and RT-qPCR to test the effects of OPZ on the overall pattern of mRNA expression of multiple metabolic pathways in human hepatocytes in primary culture. Our results show for the first time that OPZ significantly alters the expression of human genes, at both mRNA and protein levels, within different functional categories (detoxication of xenobiotics, antioxidant defences, xenobiotic transport, cell cycle and stress response), some of them being highly relevant to chemoprevention. Amongst these genes, several have never been described to be regulated by OPZ before. We also demonstrate variations in response to OPZ, depending on the individual from whom cells are derived, that might potentially contribute to differences in efficacy of chemopreventive treatments between individuals. Moreover comparison of our results with those obtained in rodent demonstrates species differences in response to OPZ for some genes underlying the importance of studies on human cells to predict the effects of chemopreventive agents.
Revised September 23, 2004
Accepted October 12, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Oltipraz regulates different categories of genes relevant for chemoprevention in human hepatocytes
Fabrice Morel, E-mail: Fabrice.Morel{at}rennes.inserm.fr
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