preneoplastic cells (6)(7)(8). However, the mitogenic signals that trigger hepatic cell replication by these non-genotoxic Alessandria Bruccoleri 2 , Robert Schoonhoven 3 , Michael I.Luster 2 and Ronald G.Thurman 4 carcinogens have not been identified. Because WY-14,643 only causes about a two-fold increase 1 Departments of Pharmacology and Curriculum in Toxicology, and in cell replication in isolated hepatocytes and a near eight-3 Environmental Sciences and Engineering, University of North

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... lina, fold elevation in vivo, it is possible that factors from non-Chapel Hill, NC 27599 and 2 Immunology and Neurobiology Section, NIEHS, RTP, NC 27709, USA parenchymal cells are responsible for high rates of cell turnover in vivo (9). It is well known that activated Kupffer cells, the 4 To whom correspondence should be addressed at: Laboratory of resident hepatic macrophages, release mitogenic and chemotac-Hepatobiology and Toxicology, Department of Pharmacology, CB# 7365, FLOB, University of North Carolina at Chapel Hill, Chapel Hill, tic factors and could theoretically be involved in regulating NC 27599-7365, USA