EFFECTS OF CARBON-TETRACHLORIDE, ETHANOL AND ACETALDEHYDE ON DIETHYLNITROSAMINE-INDUCED HEPATOCARCINOGENESIS IN RATS

The modifying action of experimentally induced chronic liver injury on diethylnitrosamine (DEN) hepatocarcinogenesis was investigated using a minimal treatment protocol. A single dose of DEN (15 mg/kg b.w.) was administered as a carcinogen to 1-day-old Sprague-Dawley rats. From 3 weeks of age rats received repeated intraperitoneal injections of carbon tetrachloride (CCl4), or 10% ethanol or 5% acetaldehyde in the drinking water for 9 weeks. Combinations of CCl4 and ethanol or acetaldehyde were also tested. Morphology, immunohistochemistry for glutathione S-transferase-placental form, and incidence and quantity of preneoplastic lesions of the livers were studied. The chronic CCl4 administration produced complete or incomplete liver cirrhosis and exerted a strong promoting effect on the development of neoplastic nodules. Ethanol alone revealed no cirrhogenous or tumor-promoting effect, but enhanced both actions of CCl4. Acetaldehyde increased only the cirrhogenous effect of CCl4.