| Summary: | 碩士 === 中國文化大學 === 生物科技研究所 === 101 === Cigarette smoke (CS) is a complex mixture of the gas and particulate phases, in which contain more than 4000 chemical compound. CS will lead to the occurrence of cancer, and damage to smokers, as well as passive smoker’s health. In a recent study of cigarette smoke, pyrazine, 2-ethylpyridine, 3-ethylpyridine were identified in cigarette smoke and shown to be the most potent chemicals in their respective groups to have the strongest effects on cells. Lung cancer is the leading cause of cancer-related mortalities in both genders and this malignancy accounts for 15% of all cancer deaths globally and this malignancy is associated with cigarette smoking. Furthermore, development of lung cancer is also accompanied with tumoral hypoxia, which has been shown to play important role in disease progression. On the other hand, drug resistance, the reduction in effectiveness of a therapeutic agent in curing a disease, is a major problem in cancer management. The purpose of this study is to investigate the effects of known cigarette smoke toxicants components on human normal and malignant tumor lung cells. Our data showed that cigarette smoke components decreased cells proliferation in normal lung cells MRC5 while induced cell proliferation in malignant tumor lung cells. When adenocarcinomic A549 cells were maintained in hypoxia, the stimulatory effect on cell proliferation was enhanced. Based on our results, the lowest observed adverse effect level (LOAEL) was determined to be at 10-10M in normaxia. When cells were administrated with cigarette smoke components at LOAEL, the percentage of viable cells was decreased in both MRC5 and A549 cells; however, the difference is only statistically significant in A549 cells. In addition, the percent of apoptotic cells detected in cultures was comparable to that of control group in both normal and malignant, suggesting that these smoke constituents impair normal cell proliferation via mechanism(s) other than cell program death. Our oxidative stress analysis data showed that cigarette smoke components caused a significant induce in the generation of intracellular H2O2, evidencing oxidative stress induction in both MRC5 and A549 cells. Furthermore, cigarette smoke components did not significant affect invasion of A549 cells in low or normal oxygen environment. Finally, these heterocyclic aromatic smoke components caused a significant decrease in the rhodamine mean intensity of A549 cells, suggesting the development of drug resistance. Taken together, the present finding reveal adverse effects of cigarette smoke components on human respiratory system.
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