Quantitative kinetics of development of N-2-fluorenylacetamide-induced, altered (hyperplastic) hepatocellular foci resistant to iron accumulation and of their reversion or persistence following removal of carcinogen

Abstract

For study of the behavior of previously described carcinogen-induced foci of hepatocytes refractory to iron accumulation, iron deposition was induced in all hepatocytes of rat livers by feeding 8-hydroxyquinoline and ferrous gluconate to the animals for 3 months. The kinetics of development of the altered foci of hepatocytes free of stainable iron was then quantified for each lobe of liver for as long as 13 weeks of feeding of the carcinogen N-2-fluorenylacetamide and for 6 months following cessation of carcinogen exposure. The foci increased slowly in number and size for the first 12 weeks of carcinogen administration and then grew rapidly between weeks 12 and 13. At week 13, they corresponded to altered foci that have been observed in sections stained with hematoxylin and eosin, and they also displayed abnormal glycogen storage. After the carcinogen was discontinued, the foci disappeared by a reversion back to iron storage while temporarily retaining the nuclear abnormalities of altered cells. Over 95% of altered foci at this stage underwent reversion by 6 months following removal of the carcinogen. More advanced lesions developed in the lobes that displayed the greatest incidence and persistence of foci.