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Comparative Carcinogenicity and Metabolism of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-Nitrosonornicotine in Syrian Golden Hamsters¹

Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595

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, three developed carcinomas of the nasal cavity, and 19 had adenomas and/or adenocarcinomas of the lung. In the NNN group, one hamster developed a lung adenoma, and five 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 seven had tracheal papillomas; in the NNN group, we recorded only one hamster with a lung adenoma and one with a tracheal papilloma. 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 to 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 to 78% in urine, 10% in feces, and less than 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 -hydroxylation, from N-oxidation of NNN to N'-nitrosonornicotine-1-N-oxide, and from reduction of NNK to 4-(methylnitrosamino)-1-(3-pyridy)butan-1-ol.

¹ This study was supported by USPHS Contract N01-CP-55666 and Grant CA-21393 from the Division of Cancer Cause and Prevention, National Cancer Institute. This is Paper 20 in the series, "A Study of Tobacco Carcinogenesis."

² To whom requests for reprints should be addressed.

Received 11/26/80. Accepted 3/13/81.

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