The influence of metabolic liver defects on diethylnitrosamine (NDEA)-carcinogenesis in Gunn rats

Diethylnitrosamine (NDEA) was administered subcutaneously to non-icteric and icteric Gunn rats. A single dose led predominantly to liver cell tumours. The average survival times and tumour latencies were not dose dependent, but a slightly raised tumour multiplicity was observed in icteric animals. The minimal effective dose was apparently less than 0.05 LD50 and more than 0.025 LD50. Chronic treatment in Gunn rats revealed dose response relationships for body weight development, average survival times and tumour latencies. The most common tumours found in the liver of both non-icteric and icteric animals were hepatocellular neoplasms followed by cholangiocellular tumours and haemangio-endotheliomas. Neoplastic growth was also found in the respiratory tract and upper digestive tract. The maximal effective carcinogenic dose for non-icteric and icteric rats was 0.1 LD50. The carcinogenic effect of NDEA in Gunn rats was only marginally influenced by the changes in the liver associated with icterus.