Liver Carcinomas Induced in Rats by Single Administration of Dimethylnitrosamine After Partial Hepatectomy

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Abstract
Female rats weighing 200 g were given a single injection of dimethylnitrosamine (DMN), 6–9 mg/kg, at a selected interval of time after partial hepatectomy, i.e., 0–2 hours, 6 hours, 24 hours (the peak time of DNA synthesis in the regenerating liver), or 31 hours (the time of maximum mitotic rate). The ratswere killed 1–2 years later. Many livers had developed distorted hemorrhagic hyperplastic nodules, and some had trabecular carcinomas. In the relatively small number of animals used,the incidence of liver cell carcinomas was highest in the rats treated with DMN 24 hours after partial hepatectomy. Four rats developed sarcomas at the site of liver excision. No rats partially hepatectomized only or receiving a single injection of DMN with dimethylformamide developed nodules or liver tumors. DMN was metabolized, although more slowly than normal, in regenerating liver. The results are consistent with the belief that replicating cells are especially sensitive to the action of carcinogens.

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