Journal Article

Differential regulation of <i>mdr</i> genes in response to 2-acetylaminofluorene treatment in cultured rat and human hepatocytes

Valérie Lecureur, André Guillouzo and Olivier Fardel

in Carcinogenesis

Volume 17, issue 5, pages 1157-1160
Published in print May 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.5.1157
Differential regulation of mdr genes in response to 2-acetylaminofluorene treatment in cultured rat and human hepatocytes

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Expression of P-glycoprotein (P-gp), the mdr gene product, was investigated in primary cultures of rat and human hepatocytes exposed to 2-acetylaminofluorene (2-AAF). Increased levels of mdrl mRNAs were evident in 2-AAFtreatedrat hepatocytes by Northern blot analysis using rat mdr gene-specific probes, while transcripts of the mdr2 and mdr3 genes were decreased and unaffected respectively. Rat hepatocytes exposed to 2-AAF were also found to accumulate doxorubicin, an anticancer drug known to be transported by P-gp, poorly, thereby demonstrating that 2-AAF-mediated mdrl induction resulted in increased P-gp activity. In contrast to their rat counterparts, human hepatocytes obtained from 10 individuals exhibited no change in both mdr1 and mdr2 mRNA levels, as well as in doxorubicin intracellular retention, in response to 2-AAF treatment, while cytochromes P-450 CYP1A1 and CYP1A2 were induced in both human and rat hepatocyte cultures. These data provide strong evidence that regulation of expression of mdr genes in liver cells in response to carcinogens such as 2-AAF is gene- and species-specific.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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