Carcinogenesis by N-nitrosohexamethyleneimine in NZO inbred mice

The carcinogenic response of NZO/BlGd inbred mice of both sexes to oral N-nitrosohexamethyleneimine (NHEX) was investigated at 2 differing dose rates, but equal cumulative doses. Mice received 52 mg NHEX (2 mg/g body wt) in drinking water over either an 8-week period (200 mg/l) or a 32-week period (50 mg/l), and were then kept for their natural lifespans. The main sites of tumorigenesis were upper alimentary tract (oropharynx, esophagus, squamous and glandular stomach) and liver. Lymphomas and biliary epithelial tumours were also induced, but lung carcinogenic response was of marginal statistical significance. In contrast to previous reports we found responses in mice very similar to the organ pattern of NHEX carcinogenesis in rats. A comparable previous study in rats found a more marked change in response pattern at the 2 NHEX dose rates but total doses differed by up to 1.6 times in that experiment. With equal total doses of NHEX the mouse tumour patterns at the same 2 dose rates were nearly the same, but there were higher incidences of liver and lung tumours and of lymphomas at the high dose rate, in agreement with the rat study. There were no significant sex differences in carcinogenic response.