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BLOCKAGE OF A-1 ADRENERGIC RECEPTOR INHIBOTS HEPATIC DNA SYNTHESIS STIMULATED BY TUMOR PROMOTERS
Citation:
Tsai, W., J. Cruise, AND G. Michalopoulos. BLOCKAGE OF A-1 ADRENERGIC RECEPTOR INHIBOTS HEPATIC DNA SYNTHESIS STIMULATED BY TUMOR PROMOTERS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/201.
Description:
Studies with regenerating liver and hepatocyte cultures have shown that the a-1 adrenergic receptor (A1AR) is involved in the early events which transmit a mitogenic signal to hepatocytes after 2/3 partial hepatectomy. n this study, we investigated the role of A1AR in DNA synthesis associated with the augmentative hyperplasia stimulated by the xenobiotic hepatic tumor promoters phenobarbital (PB) and a-hexachlorocyclohexane (a-HCH), and the peroxisome proliferator ciprofibrate. Male F344 rats were treated with each of the three xenobiotics to stimulate hepatic DNA synthesis. hen either phenobarbital or a-HCH administration was preceded and accompanied by the A1AR antagonish prazosin, DNA synthesis was significantly inhibited, as measured by [3H]thymidine incorporation or 5-bromo-2'-deoxyuridine (BrdU) nuclear labeling index. here was no inhibition of DNA synthesis by prazosin in the ciprofibrate trated group. heinhibition of heaptic DNA synthesis by prazosin was accompanied by non-significant changes in the number of a-1 binding sites in the PB and a-HCH treated groups, but a significantly reduced number of a-1 binding sites in the ciprofibrate treated group. hese studies suggest that A1AR is involved in generating the mitogenic signal leading to hepatic DNA synthesis induced by xenobiotic hepatic tumor promoters phenobarbital and a-HCH. 1AR is not involved in the mitogenic pathway generated by the peroxisome proliferator ciprofibrate.