New aspects of tobacco carcinogenesis

In tobacco smoke, catechols represent a major group of cocarcinogens. Model studies have indicated that polyphenols and polysaccharides are two major groups of precursors for the catechol formation during smoking. Results from the application of BP together with catechol on mouse skin indicate that the detoxification path of BP metabolism is decreased and the formation of the BP-7,8-diol is increased in comparison to the metabolism pattern observed when BP is applied alone. It remains to be demonstrated that the increased BP-7,8-diol formation leads also to increased formation of BP-DNA adducts in epithelial tissues. The nicotine-derived N-nitrosamines represent a major group of carcinogens in chewing tobacco, snuff, and tobacco smoke. Their concentrations in processed tobacco and smoke exceed by far those of carcinogenic nitrosamines in other environmental materials. Whereas it has been shown that nicotine gives rise to NNN and NNK during tobacco chewing, the endogenous formation of these potent carcinogens upon smoke inhalation has so far not been demonstrated. However, the formation of N-nitrosoproline in cigarette smokers and snuff dippers proves that smoke and snuff have a measurable potential for the endogenous formation of carcinogenic nitrosamines. Finally, the data presented here indicate that the individuals subjected to passive smoke exposure under controlled conditions take up measurable amounts of particulate matter. The nicotine level in the saliva of nonsmokers reflect recent passive smoke exposure and levels of nicotine and cotinine in urine reflect the long-term exposure to smoke particulates. The indicators, measured in saliva and serum, make it clear that uptake of particulates due to passive smoke exposure corresponds only to a low percentage (less than 2%) of the particulates that represent the uptake of a 1 pack-a-day adult smoker. However, in special settings, such as in the exposure of infants to the smoke pollutants generated by their mothers, uptake of smoke constituents can reach levels which raise concerns as to possible long range toxic effects. A broader base of subjects and a wider range of pollution situations need to be tested in order to substantiate the significance of the dosimetry of uptake executed to date. Such measurements constitute an attempt at more accurate risk assessment for nonsmokers in smoke polluted environments.