Comparative carcinogenicity in F344 rats and Syrian golden hamsters of N'-nitrosonornicotine and N'-nitrosonornicotine-1-N-oxide.

N'-Nitrosonornicotine (NNN) or N'-nitrosonornicotine-1-N-oxide (NNN-1-N-oxide), one of its metabolites, was added to the drinking water (0.012% for 36 weeks) of groups of male and female F344 rats or to the drinking water (0.016% for 31 weeks) of groups of male and female Syrian golden hamsters. All rats treated with NNN had died after 12 months but 50% of those treated with NNN-1-N-oxide survived for 22 months. NNN induced esophageal tumors in 23/24 rats and nasal cavity tumors in 21/24 rats. NNN-1-N-oxide induced esophageal tumors in 10/24 rats and nasal cavity tumors in 18/24 rats. There was no difference in survival rates among hamsters treated with either NNN or NNN-1-N-oxide. NNN induced tracheal tumors in 2/20 hamsters and nasal cavity tumors in 4/20 hamsters. NNN-1-N-oxide did not induce respiratory tract tumors in hamsters. These results demonstrate that NNN-1-N-oxide is less carcinogenic than NNN in F344 rats and Syrian golden hamsters.