DOSE DEPENDENCE OF DIETHYLNITROSAMINE-INDUCED NUCLEAR ENLARGEMENT IN EMBRYONAL TURKEY LIVER

Avian embryos (turkey) were exposed to diethylnitrosamine in ovo. On t he first day of incubation doses of 0.5-5.0 mg/egg were injected into the white of the fertilized egg, The experiment was terminated 4 days before hatching. Livers were removed and prepared for subsequent histo logical examination. In haematoxylin and eosin stained sections the ar eas of hepatocyte nuclear profiles were measured by semi-automatic ima ge analysis. In liver samples of diethylnitrosamine-exposed embryos he patocyte nuclei of more than twice the size of normal hepatocyte nucle i were found. The incidence of the enlarged nuclei was clearly dose de pendent. An increase in the size of hepatocyte nuclei was observed aft er low doses of diethylnitrosamine that did not induce common signs of non-specific toxic effects, e.g. cell death, fat vacuoles or loss of glycogen. The slope of the dose-response curve was rather steep. A 10- fold increase in the dose of the carcinogen resulted in a 100-fold inc rease in the incidence of enlarged hepatocyte nuclei. In combination w ith preneoplastic foci of altered hepatocytes, the quantification of n uclear enlargement can provide a valuable complementary parameter for the evaluation of carcinogen-induced effects in ovo.