Carcinogenicity tests of methyl-n-amylnitrosamine (MNAN) administered to newborn and adult rats and hamsters and adult mice and of 2-oxo-MNAN administered to adult rats

Abstract

We examined the toxicity and carcinogenicity in rodents of methyl-n-amylnitrosamine (MNAN), multiple doses of which are known to induce esophageal and nasal tumors in rats. A single i.p. injection of 50-70 mg MNAN/kg into adult rats produced a 74% incidence of esophageal squamous carcinomas (mean latency, 63 weeks). Single doses of 3.0-12.5 mg/kg of MNAN injected into newborn and 3-day-old rats and hamsters were not carcinogenic in rats and only weakly carcinogenic in hamsters. The low doses (used because larger doses produced lethal interstitial pneumonia) probably explain the low carcinogenicity, despite previous findings of extensive formation of stable hydroxy-MNANs from MNAN by the esophagus of both species at these ages, which may indicate MNAN activation. One i.p. injection of 70-100 mg MNAN/kg into adult Syrian hamsters was weakly carcinogenic for the esophagus and forestomach. Six injections of 75 mg MNAN/kg into adult hamsters induced lung and nasal cavity tumors (65 and 43% incidences, respectively), but only a few esophageal tumors. Three injections of 15 mg MNAN/kg into adult Swiss mice induced lung adenomas and esophageal papillomas in 71 and 32% incidences, respectively. These results partially agreed with previous studies on hydroxy-MNAN formation by the esophagus of these species. Six s.c. injections of 75 mg 2-oxo-MNAN/kg into adult rats induced tumors of the nasal cavity, esophagus and soft tissue at the injection site in 68, 63, and 32% incidences, respectively. This does not support the view that 2-oxo-MNAN is an active metabolite of MNAN.