Comparative carcinogenicity in F344 rats of the tobacco-specific nitrosamines, N'-nitrosonornicotine and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone

Abstract

The tobacco-specific carcinogens, N'-nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), were tested for carcinogenicity in F344 rats. Each nitrosamine in trioctanoin was administered by s.c. injection to 12 male and 12 female rats over a period of 20 weeks. The total dose of each nitrosamine was 3.4 mmol. The experiment was terminated after 12 months. NNK induced nasal cavity tumors in 83% of the males and in 83% of the females, liver tumors in 83% of the males and in 100% of the females, and lung tumors in 67% of the males and in 67% of the females. NNN induced nasal cavity tumors in 92% of the males and in 75% of the females. Only one liver tumor and no lung tumors were observed in the NNN-treated rats. These results indicate that, in the F344 rat, NNK is a more powerful carcinogen than is NNN.