Strain and sex differences in N-nitrosohexamethyleneimine carcinogenesis in NZB, NZC, NZO, and NZY mice

Abstract

The carcinogenic activity of N-nitrosohexamethyleneimine [(NHEX) CAS: 932-83-2; hexahydro-1-nitroso-1H-azepine] was studied in male and female mice of the four inbred strains NZB/BlGd, NZC/BlGd, NZO/BlGd, and NZY/BlGd. A total of 158 mice received NHEX treatment; 1,338 untreated controls were used, all kept under identical laboratory conditions for their natural life-spans. Beginning at age 50 days a 1.56-mM NHEX solution (200 mg/liter) was given instead of drinking water for 8 weeks, which resulted in nearly the same total dosage of 0.7 +/- 0.04 g or 5.7 +/- 0.2 mmol NHEX/kg body weight in both sexes of all four strains. In both sexes of all four strains the main types of tumors after NHEX treatment were squamous papillomas and carcinomas of the esophagus, squamous stomach, and oropharynx and hepatocellular carcinomas. Tumors of the hepatic bile ducts, glandular stomach, and lung and malignant lymphomas were also induced by NHEX, but these tumors had a predilection for certain strains only. The incidences of other tumors characteristic of the untreated mice in each particular strain, such as tumors of the ovary in NZC, tumors of the breast in NZY, and tumors of the duodenum in NZO, were not increased significantly by NHEX treatment. The incidence of main tumor types in NHEX-treated mice varied greatly between strains, e.g., esophageal papillomas and carcinomas in 81% of male NZC versus 32% in male NZB mice. Some marked sex differences also emerged in NHEX-treated animals, e.g., the occurrence of liver angiosarcomas only in males of three strains and the 53% incidence of hepatocellular tumors in male NZY mice compared to the absence of liver tumors in female NZY mice.