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Biochemical and Molecular Actions of Nutrients

Exogenous Nucleosides Stimulate Proliferation of Fetal Rat Hepatocytes¹

María José Sáez-Lara, Manuel Manzano^*, Antonio José Angulo^*,2, Antonio Suárez^*, María Isabel Torres, Carolina Gómez-Llorente^**, Ángel Gil and Luis Fontana³

Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Granada, Spain; ^* R & D Department, Abbott Laboratories, Granada, Spain; Department of Experimental Biology, School of Sciences, University of Jaén, Spain; ^** Department of Biochemistry and Molecular Biology, School of Medicine, University of Granada, Spain

³To whom correspondence should be addressed. E-mail: fontana{at}ugr.es.

Exogenous nucleotides (NT) have been reported to exert a reparative role in animal models of intestinal and hepatic damage. Thus, the administration of NT in the diet of rats with thioacetamide-induced liver cirrhosis normalized many of the histological and biochemical alterations produced by this hepatotoxin. We are currently studying the mechanism by which NT exert this effect using cell culture models. The aim of this work was to investigate whether exogenous nucleosides (NS) modulate the proliferation of hepatocytes. We used fetal rat hepatocytes, which, unlike adult hepatocytes, are proliferative cells. Fetal rat primary hepatocytes were incubated with mixtures of NS, and cell proliferation was studied. NS added to the medium of fetal hepatocytes were taken up in a selective fashion by the cells. Cell proliferation was enhanced, as demonstrated by the induction of c-myc and h-ras gene expression as well as by the higher percentage of cells in S phase, and exogenous NS increased the expression of -fetoprotein. These results suggest that exogenous NS may in fact stimulate proliferation of hepatic cells and help preserve the undifferentiated state of fetal rat hepatocytes.

KEY WORDS: • exogenous nucleosides • fetal hepatocytes • proliferation • rats

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