Sexual difference in the histochemical characteristics of "altered cell foci" in the liver of aged Fischer 344 rats.

The distributions of gamma-glutamyltransferase (GGT) and the placental form of glutathione S-transferase (GSTP) were examined in the livers of 18-month-old and 23-month-old SPF F344/DuCrj rats of both sexes. The number of the enzyme-altered foci in males was greater than in females, and it increased with age in animals of both sexes. Histologically, most of the foci in males consisted of eosinophilic or clear hepatocytes, while those in females were predominantly basophilic. More than 75% of the foci in males stained positively for GGT and GSTP. In contrast, more than 80% of the foci in females were GGT- and GSTP-negative. Thus, though both enzymes have been widely used for analysis of carcinogen-induced hepatocarcinogenesis, it appears that GGT and GSTP are inappropriate as markers of preneoplastic lesions in natural hepatocarcinogenesis in female rats.