KINETICS OF DIETHYLNITROSAMINE HEPATOCARCINOGENESIS IN THE INFANT MOUSE

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (9) , 4253-4259
Abstract
Kinetics of hepatocarcinogenesis was evaluated in 15-day-old male C57BL/6J .times. C3HeB/FeJ F1 mice using a nontoxic carcinogenic dose range of diethylnitrosamine (DEN). The carcinogen was injected i.p. once, and the animals were killed according to the protocol. Two studies were carried out sequentially over a period of 4 yr. In the 1st study, groups of mice were treated with 0.625, 1.25, 2.5 and 5.0 .mu.g of DEN/g body wt, and subgroups of 8 mice were killed at 10-wk intervals, the 1st at 10 wk following carcinogenic treatment. The dose-response relationship, transformation probabilities and the dose vs. time to 50% incidence of the early (basophilic foci) and later appearing focal and nodular hepatocellular lesions were evaluated. In the 2nd study, groups of mice were treated with 0.312, 0.625, 1.25, 2.5 and 5.0 .mu.g of DEN/g body wt, and subgroups of 8-20 animals were killed at 10, 16, 20, 24, 30, 34, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 and 110 wk after carcinogenic treatment. The numbers of induced basophilic foci and hepatocelluar carcinomas per number of liver cells at risk (transformation probabilities) were used to evaluate dose-response, time-response and time-dose kinetics. In both studies, the kinetics of hepatocarcinogenesis was evaluated from data plotted on the double log scale. At least 2 critical events evidently are needed for the induction of basophilic foci and at least 4 events are required for the induction of hepatocellular carcinomas. Difference in the kinetics and in the transformation probabilities between the basophilic foci and the heptocellular carcinomas indicates that basophilic foci cannot be used as direct indicators of development of hepatocellular carcinomas.