Summary and Conclusions
A cigarette tar condensate was obtained with a smoking machine which simulated human smoking habits. The resulting tar was dissolved in acetone and applied to the backs of CAF1 mice in a dosage of 40 mg. of tar/acetone solution 3 times a week. Control mice were painted with acetone.
Of 81 tarred mice, 59 per cent developed papillomas. The first lesion was noted in the 33d week, and the mean time of appearance was 56 weeks.
Of 81 tarred mice, 44 per cent developed histologically proved carcinomas. The first carcinoma was observed in the 42d week, and the average time of appearance was 71 weeks. Of 62 mice alive at 12 months, 58 per cent developed cancer. Seventy-one weeks constitutes approximately one-half of the life span of CAF1 mice. This corresponds roughly with the fact already noted that in the human about 30–35 years of smoking, or approximately one-half the life span, are required for the production of bronchiogenic carcinoma.
One carcinoma was transplanted for 4 generations and another one is currently growing in the 13th generation.
Control mice painted with acetone alone showed no skin lesions. At the end of 20 months of painting, 53 per cent were still living, compared to 9.8 per cent in the group painted with tobacco tars.
The group of mice painted with croton oil in addition to the tar, starting in the 7th month, cannot be properly evaluated because of a greater number of deaths occurring during the 12th and 14th months, although within the period of observation no acceleration of cancer formation was noted.
The group of mice started with acetone and receiving croton oil beginning in the 7th month showed roughening and thickening of the epidermis, but no tumor formation was noted.
All CAF1 mice painted with 0.3 per cent solution of methylcholanthrene in acetone developed cancer within 4½ months. The first papilloma appeared during the 6th week, with average appearance during the 7th seek. The first carcinoma was observed during the 12th week, with a mean time of appearance of 16 weeks.
The results obtained with CAF1 mice establish condensed cigarette tar as a carcinogen for mouse epidermis. These studies provide a tool to determine and isolate the possible carcinogenic agent(s) within tobacco tar. At present it is not known which fraction or fractions in tobacco tars are carcinogenic. Combined chemical and biologic studies are now in progress to search for such agents. Such studies, in view of the corollary clinical data relating smoking to various types of cancer, appear urgent. They may result not only in furthering our knowledge of carcinogenesis, but in promoting some practical aspects of cancer prevention.
This investigation was supported by a research grant from the National Cancer Institute of the National Institutes of Health, Public Health Service.