Liver carcinogenesis by diethylnitrosamine in the rat

Diethylnitrosamine was continuously administered to rats at a dose rate of low toxicity. Ninety-two percent of the animals died with multicentrical hepatocellular carcinomata within a narrow and highly reproducible time interval. Discontinuing the carcinogen during the experiment resulted in a prolonged median time until death, a reduced tumor yield, and a lessened slope of the dose-response curve. Partial hepatectomy after discontinuation of the drug did not change either tumor yield or time of death. The obtained dose-response relationships support the concept that carcinogenic effects of single doses are irreversible and cumulative. Daily, low-dose, total-body x-irradiation had no significant effect on the response of rat liver to the carcinogen.