Abstract
The development of hepatocellular carcinoma in rats by chemicals is a long-term process in which discrete focal populations of new hepatocytes and other liver cells appear regularly and quite reproducibly. Included among the cellular changes are “oval cell proliferation” (1,2), foci or islands of altered hepatocytes (3–6), hepatocyte nodules (“hyperplastic” or “neoplastic” nodules or “adenomas”) (7,8), and, later, nodules (persistent nodules) that appear to be closely associated with the precancerous steps of hepatocellular carcinoma (9–12). As with any cells showing new biological behavior, these new hepatocytes and other liver cells are associated with altered phenotypic expression. These are recognized as altered “phenotypic markers” during the carcinogenic process.
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