Nature of early appearing, carcinogen-induced liver lesions to iron accumulation.

A technique for induction of iron accumulation in hepatocytes of rats was used to identify early carcinogen-induced lesions by their histochemical absence of iron. Foci of iron-free altered hepatocytes produced by the feeding of N-2-fluorenylacetamide (FAA) for 3 weeks were composed of cells that were replicating when surrounding iron-containing hepatocytes were not, and that responded to a mitotic stimulus when surrounding hepatocytes were inhibited or showed a delayed response. Thus these lesions represented focal hyperplastic overgrowths. The iron-free hyperplastic foci developed into hyperplastic areas that progressed with longer feeding of FAA to form hyperplastic nodules. The lack of iron was a sensitive and reliable marker for hyperplastic lesions, which also permitted their identification in the fresh state. Both early hyperplastic lesions and nodules were often resistant to the necrogenic effects of dimethylnitrosamine, as well as to the antireplicative effect of FAA. The selection of such cells resistant to the toxic effects of carcinogens may be important in the pathogenesis of liver neoplasia.