A possible role for dihydrodiol dehydrogenase in the formation of benzo[a]pyrene-DNA adducts in lung cancer cells and tumor tissues

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 健康照護學院 > 二年制呼吸治療學系 > 期刊論文 > Item 310903500/6373

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题名:	A possible role for dihydrodiol dehydrogenase in the formation of benzo[a]pyrene-DNA adducts in lung cancer cells and tumor tissues
作者:	(Ya-Wen Cheng);(Horng-Jyh Tsai);(Jeng-Yuan Wu);(Yi-Feng Hsu);陳志毅(Chih-Yi Chen);(Nina-Jyu Hao);(Huei Lee)
贡献者:	健康照護學院二年制呼吸治療學系學士班在職專班;中國附醫癌症中心
关键词:	dihydrodiol dehydrogenase;nonsmall cell lung cancer;DNA damage
日期:	2007
上传时间:	2009-08-25 15:49:12 (UTC+8)
摘要:	Epidemiological studies indicate that there is a gender difference in the susceptibility to tobacco and environmental carcinogens, and this gender difference is suspected to result in a higher risk for lung cancer among women. However, the molecular mechanisms underlying this sexual dimorphism remain unclear. In the present study, we have evaluated the roles of CYP1A1 and dihydrodiol dehydrogenase (DDH) in the formation of benzo[a]pyrene (BaP) DNA adducts in various lung cancer cell lines. Among six lung cancer cell lines tested, higher adduct levels were observed in CL-3 and CL1-1 cells, which had relatively high expression of both CYP1A1 and DDH isoform 1 (DHH1). To determine whether a reduction in DDH expression changed the adduct levels, an siRNA was used to knock down DDH1 expression in CL-3 cells. The BaP adduct levels in siDDH-CL-3 cells increased 1.4-2.2-fold relative to that of the parental CL-3 cells. We also examined BaP-like DNA adducts, and CYP1A1 and DDH1 expression by immunohistochemistry in 120 lung tumors. Detection of DNA adducts correlated with CYP1A1-positive tumors (P = 0.023), but not with DDH1-positive tumors. In addition, 28 of 33 tumors (85%) that were CYP1A1-positive and DDH1-negative contained detectable levels of DNA adducts, a proportion that was higher than for tumors from the other three categories of CYP1A1 and DDH1 expression (P = 0.012). Finally, a greater proportion of adduct-positive tumors from females were CYP1A1-positive/DDH1-negative (45.3%) than were tumors from males (27.3%). These results suggest that the reduction of DDH expression in lung tumors may contribute to an increase in DNA adduct levels, which may be partly responsible for the higher susceptibility of female lung cancer patients to DNA damage. Environ. Mol. Mutagen.
關聯:	ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 48(1)14 ~21
显示于类别:	[二年制呼吸治療學系] 期刊論文

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