Lack of Proportionality between Rate of Cell Division and Induction of Tumors in Carcinogen-exposed Regenerating Livers¹

Although a single pulse of dimethylnitrosamine administered during the regenerative response of liver subsequent to 70% hepatectomy resulted in more primary hepatocellular carcinomas in treated livers than in controls, the response was not proportionate to the level of cell division. Further, the use of 55-g male Sprague-Dawley rats that displayed an extremely active regenerative response did not significantly shorten the lag period before the appearance of tumors. Of additional interest was the finding that the post-S period might be even more susceptible to dimethylnitrosamine than the S phase was. These results support the suggestion that many aspects of the interaction between carcinogens and dividing cells and the requirement for subsequent events for the development remain unclear.