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

3 Epidemiological studies indicate that the risk of cigarette smokers for cancer of the lung and of the pancreas is influenced by the fat co ntent of the daily diet. In a long-term bioassay (24 months), we gave F344 rats 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a toba cco-specific and strongly carcinogenic N-nitrosamine, as a 2 ppm solut ion 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 con trol 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 receivin g the low-corn oil diet and tap water (LF). Eighteen months into the b ioassay, 16 of 60 rats in the NNK-HF group had developed lung tumors a veraging 6.8 mm2, while 3 of 60 rats in the NNK-LF group had tumors av eraging 2.5 mm2. At the termination of the experiment after 24 months, the numbers ot rats with lung tumors in the NNK-HF and NNK-LF groups did not significantly differ from each other, nor was there a differen ce in the size of the lung tumors. The effect of dietary fat on the pa ncreas 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 h ad 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 i n each of the control groups (HF and LF) had developed pancreas tumors . In fact, there was an increasing trend of development of pancreas tu mors in these control rats with aging regardless of dietary fat varian ce. However, in view of the observed tumor acceleration and enhancemen t this study points to the importance of evaluating both exposure to t obacco carcinogens and dietary fat intake as risk factors for tobacco users.