A STUDY ON TOBACCO CARCINOGENESIS .20. COMPARATIVE CARCINOGENICITY AND METABOLISM OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE AND N'-NITROSONORNICOTINE IN SYRIAN GOLDEN-HAMSTERS
The tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N''-nitrosonornicotine (NNN) were tested for carcinogenic activity in Syrian golden hamsters. In assay A, 30 hamsters were each given 19 s.c. injections of 0.048 mmol of NNK or NNN. In assay B, 20 hamsters each received 75 s.c. injections of 0.012 mmol of NNK or NNN. Among the NNK-treated hamsters in assay A, 3 developed carcinomas of the nasal cavity, and 19 had adenomas and/or adenocarcinomas of the lung. In the NNN group, 1 hamster developed a lung adenoma and 5 had tracheal papillomas. In assay B, 11 of the NNK-treated hamsters developed carcinomas of the nasal cavity, 16 had lung adenomas and/or adenocarcinomas and 7 had tracheal papillomas; in the NNN group, only 1 hamster with a lung adenoma and one with a tracheal papilloma were recorded. These findings in the Syrian golden hamster confirm that NNK is a more powerful carcinogen than NNN, as was shown previously in assays with rats and mice. In metabolism studies, 96-98% of the radioactivity of the injected [1-14C]NNK was recovered in the urine, 4% was recovered in the feces and less than 0.5% was recovered as exhaled 14CO2. The corresponding distribution for [2''-14C]NNN was 62-78% in urine, 10% in feces and < 0.5% in respiratory 14CO2. The levels of binding of [1-14C]NNK and [2''-14C]NNN to the trichloroacetic acid-insoluble fractions were highest in liver, lung, kidney and adrenals. The urinary metabolites of NNK and NNN resulted from .alpha.-hydroxylation, from N-oxidation of NNN to N''-nitrosonornicotine-1-1N-oxide and from reduction of NNK to 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol.