EXPERIMENTAL AND MOLECULAR PATHOLOGY 51, 97-102 (1989) Variations of Serum Lipoproteins during Cell Proliferation Induced by Lead Nitrate S. DESS~,’ B. BATETTA,’ A. CARRUCCIU,’ D. PULISCI,’ S. LACONI,’ A. M. FADDA,* C. ANCHIN,* AND P. PANI’ ‘Istituto di Farmacologia e Patologia Biochimica, ‘Istituto di Chimica Farmaceutica Tossicologica ed Applicata, University of Cagliari, Via Porcell, 4, 09124 Cagliari, Italy Received July 25, 1988, and in revised form April 4, 1989 In the present study serum lipoproteins were investigated during cell proliferation induced by a potent mitogen, lead nitrate. A strong decrease in HDL, and a concomitant increase in HDL, were observed in lead-treated rats. The recovery of normal lipoprotein pattern took place together with the regression of hyperplastic process. Since a decrease in HDL also occurs under other conditions of cell growth, we hypothesize that a decrease in HDL, mainly in HDL, subfraction, may represent a generalized phenomenon related to massive cell proliferation. 0 1989 Academic Press. Inc. INTRODUCTION Cholesterol is a constitutive molecule of cell membranes; due to this property it can modulate several biological functions, including cell proliferation (Coleman and Lavietes, 1981). Intracellular cholesterol metabolism is greatly affected by circulating serum cholesterol carried by lipoproteins. It is well known that low density lipoproteins (LDL) inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, the first limiting en- zyme of the cholesterol biosynthetic pathway (Goldstein and Brown, 1977). Such a process occurs through a receptor-mediated mechanism by which serum cho- lesterol is able to influence intracellular synthesis (Goldstein and Brown, 1977). Reversely, it is conceivable that the intracellular cholesterol pool may affect cholesterol composition in serum. Proliferating tissues, including tumoral tissues, are characterized by an in- creased cholesterogenesis and by an accumulation of cholesterol esters (Fex and Wallinder, 1973; Rao et al., 1983; Pani et al., 1984). These findings raise the question whether intracellular modification of cholesterol metabolism during cell proliferation may also affect the composition of cholesterol carrying lipoproteins. An alteration of serum lipoproteins, mainly due to a decrease in high density lipoprotein (HDL) levels, was previously shown in our laboratory to occur during liver regeneration after partial hepatectomy (Dessi et al., 1986). It was suggested that these changes could be due to a greater utilization and storage of cholesterol in proliferating tissues for membrane biogenesis. However, an impaired lipopro- tein secretion due to a reduced liver mass could not be ruled out. In the present study lipoprotein metabolism was investigated in serum of rats treated with a single administration of a potent mitogen for liver and kidney, lead nitrate (Columbano et al., 1983). Oppositely to liver regeneration following partial hepatectomy, lead nitrate- induced cell proliferation is not a consequence of parenchymal loss, but is rather a process characterized by a net tissual gain with no apparent sign of cell injury (Columbano et al., 1983; Ledda-Columbano et al., 1987). 97 0014-4800/89 $3.00 Copyright 0 1989 by Academic Press, Inc. All tights of reproduction in any form reserved.