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A Study of Tobacco Carcinogenesis: Effect of the Fat Content of the Diet on the Carcinogenic Activity of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in F344 Rats^{1, ,2}

Naylor Dana Institute for Disease Prevention, American Health Foundation [D. H., A. R., E. L. W.], and the Department of Pathology, New York Medical College [R. A.], Valhalla, New York 10595

3 Epidemiological studies indicate that the risk of cigarette smokers for cancer of the lung and of the pancreas is influenced by the fat content of the daily diet. In a long-term bioassay (24 months), we gave F344 rats 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific and strongly carcinogenic N-nitrosamine, as a 2 ppm solution in the drinking water. One group of rats was given a high-corn oil diet (23.5%), and the second group received a low-corn oil diet (5.0%). The animals on the high-corn oil diet and NNK (NNK-HF), and the control animals on the same diet but on tap water (HF) had significantly higher body weights and shorter life spans than the rats on a low-corn oil diet and NNK (NNK-LF) and the corresponding control rats receiving the low-corn oil diet and tap water (LF). Eighteen months into the bioassay, 16 of 60 rats in the NNK-HF group had developed lung tumors averaging 6.8 mm², while 3 of 60 rats in the NNK-LF group had tumors averaging 2.5 mm². At the termination of the experiment after 24 months, the numbers of rats with lung tumors in the NNK-HF and NNK-LF groups did not significantly differ from each other, nor was there a difference in the size of the lung tumors. The effect of dietary fat on the pancreas tumor incidence was more pronounced. After 18 months, 11 of 60 rats treated with NNK-HF but only one of 60 rats treated with NNK-LF had developed pancreas tumors. At the termination of the study, 28 NNK-HF-treated rats had pancreas tumors (17.5 ± 13.5 mm) compared to 19 NNK-LF-treated rats (9.6 ± 11.7 mm²). After 24 months 6 of 20 rats in each of the control groups (HF and LF) had developed pancreas tumors. In fact, there was an increasing trend of development of pancreas tumors in these control rats with aging regardless of dietary fat variance. However, in view of the observed tumor acceleration and enhancement this study points to the importance of evaluating both exposure to tobacco carcinogens and dietary fat intake as risk factors for tobacco users.

¹ Supported by USPHS Grant CA29580 from the National Cancer Institute.

² Dedicated to Professor Rolf Preussmann on the occasion of his sixty-fifth birthday.

³ To whom requests for reprints should be addressed, at Naylor Dana Institute for Disease Prevention, American Health Foundation, One Dana Road, Valhalla, NY 10595.

Received 11/23/92. Accepted 4/ 7/93.

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