SENSITIVITY AND HETEROGENEITY OF HISTOCHEMICAL MARKERS FOR ALTERED FOCI INVOLVED IN LIVER CARCINOGENESIS

Abstract

S.c. injection of Fe dextran resulted in a hepatic siderosis within 2 wk in rats, as previously reported for mice. Hepatic carcinomas as well as neoplastic nodules in rats were entirely or mainly free of stainable Fe and could be readily identified histologically. Early carcinogen-induced altered foci were resistant to Fe accumulation. In rats fed 0.02% N-2-fluorenylacetamide (FAA) for 13 wk, the number of Fe-resistant foci identified following Fe injection was the same as that observed with dietary Fe overload. Histochemical investigation of enzymatic markers that were used to identify foci in rats revealed that foci characterized by enzymatic reactions of positive .gamma.-glutamyl transpeptidase and decreased adenosine triphosphatase and glucose-6-phosphatase corresponded to those characterized by resistance to Fe accumulation. In quantitative analysis of the early carcinogen-induced foci in rats given Fe dextran following a diet containing 0.02% 2-FAA for 13 wk, more lesions were detected by resistance to Fe accumulation than by any of these other properties. There was considerable phenotypic heterogeneity among foci for the enzyme markers. Resistance to Fe accumulation is a more sensitive and reliable marker for early carcinogen-induced altered hepatocellular foci than is any other histochemical property.