Age-, sex-, and strain-dependent differences in the induction of enzyme-altered islands in rat liver by diethylnitrosamine

The formation of foci with loss of ATPase and emergence of γ-GTase was studied histochemically in livers of male and female Wistar and Sprague-Dawley rats of 3-4 and 6-7 weeks of age, respectively, after application of diethylnitrosamine. A single dose of 8 mg/kg body weight induced a considerable island formation in weanlings of both sexes. Island induction in adults was observed only after repeated application. No difference in island size and number was observed with the exception of greater island size in Sprague-Dawley females. Sex-dependent differences in susceptibility to island induction were observed in weanlings, females being more sensitive than males and Sprague-Dawley females being the most sensitive of all. No correlation was seen between monooxygenase activity and the extent of island formation. The coincidence of ATPase-deficiency and emergence of γ-GTase was highest in Sprague-Dawley females. The importance of this result in respect to cancer formation is discussed. Weanling Sprague-Dawley females seemed to be the most suitable for use in a screening test system for chemical carcinogenicity, especially for testing low doses or weak carcinogens.