Epidemiological studies have found a positive correlation between cigarette smoking and emphysema, cardiovascular disease, and cancer. However, specific components in cigarette smoke that are responsible for such activity, and the affected cells within the respiratory tract have not been identified. In this proposal, we will use a nonhuman model that has shown changes in intermediate variables related to these diseases after smoking cigarettes in a human-liker manner. The hypothesis to be tested in this proposal is that exposure to different types of cigarettes smoked under controlled conditions will cause biochemical and morphological alterations in specific types of lung cells. We will compare the toxic and genotoxic effects of smoking different types of cigarettes on cells of the bronchial epithelium (BECs), the principal target tissue for development of bronchogenic carcinoma in humans, and on pulmonary alveolar macrophages (PAMs), cells that might contribute to the development of smoking-related disease. Cigarettes containing oil of cloves are suspected of causing pulmonary edema and acute hemorrhage in otherwise healthy junvenile cigarette smokers. Eugenol, the major consitutent of clove oil, producees acute pulmonary edema in rodents similar to that observed in humans. We will determine if toxic responses in BECs and PAMs following exposure to clove cigarette smoke are greater than those observed with other cigarette types. Pulmonary function will be evaluated following exposure to known amounts of combustion products from four types of cigarettes that vary in delivery of tar, nicotine, and carbon monoxide. Both histological and biochemical endpoints will be evaluated in lung cells. To evaluate the genotoxic potential of the different types of cigarettes for BECs, similarities in DNA adduct profiles and persistence of specific DNA adducts will be correlated with extent of exposure. The ability of BECs to transport mutagens to adjacent cells will be evaluated in a V79 cocultivation assay. This approach, where exposure can be controlled and quantitated, will provide information for further studies to identify components in the combustion of tobacco that have specific effects (toxic or genotoxic) on various cell types in the lung.
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