本計劃第二年研究結果中發現肺癌患者肺組織中之DNA鍵結物含量遠高於非肺癌患者，且抽菸並不會影響 DNA鍵結物的形成，這結果再次印證台灣地區肺癌患者肺組織中BaP-DNA 鍵結物的形成可能主要來自環境暴露。本年度將進一步比較不抽菸男女性肺癌患者肺組織中之DNA鍵結物含量，以釐清女性對環境污染物是否有較高之感受性？本年度以ELISA及32P-Postlabeling兩種方法分析62 位不抽菸之肺癌患者及20位不抽菸之非肺癌患者肺組織中DNA 鍵結物之含量，希望能藉此釐清空氣污染與肺癌形成之相關性。結果發現肺癌患者肺組織中的DNA 鍵結物含量遠高於非肺癌之控制組，且在不抽菸女性肺癌患者非腫瘤組織中之DNA鍵結物含量亦高於不抽菸之男性肺癌患者。而不抽菸之男、女性肺癌患者在形成及代謝毒物之CYP1A1 及GST-M1 基因之多形性及蛋白表現上則沒有差異，這結果更進一步顯示女性可能對環境污染物有較高之感受性。這結果可能可以用來解釋為什麼女性不抽菸但有高肺癌發生率的原因。 In last year project, our data showed that DNA adduct levels of lung cancer patients were significantly higher than non-cancer control and no difference in adduct levels between smoking and non-smoking lung cancer patients. These results suggest that environmental factors other than smoking may play an important role in lung cancer development in female nonsmokers. The purpose of this study was to elucidate the role of environmental carcinogen exposure in lung cancer development in Taiwanese nonsmokers, based on DNA adduct formation. We collected non-tumorous lung tissues resected from sixty-two nonsmoking lung cancer patients and twenty non-cancer controls to investigate whether differences in susceptibility to DNA adduct formation exist between men and women. 32P-Postlabeling and ELISA (enzyme-linked immunosorbent assay) with polyclonal antibody against BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene)-DNA adduct were used to evaluate DNA adduct levels in lung tissues of study subjects. Our data showed that the DNA adduct levels of lung cancer patients determined by both assays were significantly higher than those of non-cancer controls. Moreover, DNA adduct levels in females were markedly greater than in males. The difference in DNA adduct levels could not be explained by genetic polymorphisms of cytochrome P-4501A1 (CYP1A1) or glutathione S-transferase (GSTM1), as determined by polymerase chain reaction and restriction fragment length polymorphism. These results demonstrate that lung cancer patients have a higher susceptibility to DNA damage than non-cancer controls. In addition, differences in susceptibility to DNA damage derived from environmental carcinogen exposure were observed between male and female nonsmokers. In conclusion, high susceptibility to DNA damage in females may partially explain the high mortality rate of lung cancer in nonsmoking Taiwanese women.
