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.
Bibliographical noteFunding Information:
We thank Mary Jacobs for her excellent technical assistance. This study was supported by National Cancer Institute Grant No. CA-21393.