Sequential cellular changes during chemical carcinogenesis.

Phenotypically altered, preneoplastic cell populations were detected by micromorphological and cytochemical methods in a number of tissues treated with various chemical carcinogens. Further cellular analysis of carcinogenesis has shown that different cellular phenotypes follow each other during tumor development. Thus, stages of the neoplastic transformation leading from preneoplastic to early and advanced neoplastic cells can be observed directly. The cellular changes preceding the various tumor types suggest that cytologically different neoplasms have also a different cytogenesis. The identification of putative preneoplastic and early neoplastic cell populations by morphological and cytochemical methods allows for the first time the dissection and subsequent detailed investigation of target cells of chemical carcinogens that are at high risk of becoming cancer cells. Recent results of the cytochemical and biochemical microanalysis of preneoplastic hepatocytes support the concept that the well-known aberration of carbohydrate metabolism in tumor cells might occur in response to a carcinogen-induced metabolic derangement, which frequently appears to be associated with an excessive storage of polysaccharides or lipids persisting for weeks and months until fast-growing tumors develop. The increasing reports on the appearance of hepatic tumors in humans suffering from inborn hepatic glycogenosis agree with this hypothesis. Whereas the cause of the persisting storage phenomena is most probably fixed at the genetic level, epigenetic changes, namely an adaptation of cellular enzymes gradually activating alternative metabolic pathways, might be responsible for the ultimate neoplastic transformation of the cell.