Production of kidney tumors in rats with low dose of dimethylnitrosamine after partial hepatectomy.

The occurrence of kidney tumors in inbred Wistar rats as a result of dimethylnitrosamine (DMN) administration at different intervals after partial hepatectomy was studied. The schedule for DMN administration was determined on the basis of the levels of liver dimethylnitrosamine demethylase (DMN-d) at different intervals after the operation. DMN-d was 62% of the control values at 24 hours. 72% at 72 hours, and 96% at 92 hours after the operation. At these intervals a single dose of DMN (10 mg/kg body wt) was given to partially hepatectomized animals and to untreated controls. At termination, when the animals were 94 weeks old, no kidney tumors were found in the control animals, whereas 23 of 54 animals (43%) that had been given injections of DMN 24 hours after partial hepatectomy developed kidney tumors. Kidney tumor incidence was 28 or 12%, respectively, when the carcinogen was administered 72 of 92 hours after the operation. The kidney tumor incidence and the activity of liver DMN-d were inversely related.