Wy-14,643, a peroxisome proliferator, inhibits compensative cell proliferation and hepatocyte growth factor mRNA expression in the rat liver.
Previously, we found that a peroxisome proliferator significantly reduced hepatic and plasma hepatocyte growth factor (HGF) levels in male F-344 rats, and that the growth of preneoplastic or neoplastic cells induced by this peroxisome proliferator was markedly inhibited by HGF. Here, we examined the effects of [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643), a peroxisome proliferator, on cell proliferation and HGF mRNA levels in the liver of rats after stimulation of compensative cell proliferation. After 2 weeks of treatment with Wy-14,643, hepatic DNA synthesis caused by partial hepatectomy was decreased by 50% compared with untreated controls. DNA synthesis was maintained at the same reduced level for up to 10 weeks. During this period, hepatic HGF mRNA level was also much lower in Wy-14,643-treated rats than untreated controls. Therefore Wy-14,643, a peroxisome proliferator, would inhibit the growth of normal hepatocytes, and then produce an advantageous circumstance for the selective growth of neoplastic or preneoplastic cells.
Motoki
Y
Y
Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. ym95505@ps.toyaku.ac.jp
Tamura
H
H
Watanabe
T
T
Suga
T
T
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D002273:Carcinogens; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; C006253:pirinixic acid