Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells
	Lee, Hyun-Wook ; Wang, Hsiang-Tsui ; Weng, Mao-wen ; Hu, Yu ; Chen, Wei-sheng ; Chou, David ; Liu, Yan ; Donin, Nicholas ; Huang, William C. ; Lepor, Herbert ; Wu, Xue-Ru ; Wang, Hailin ; Beland, Frederick A. ; Tang, Moon-shong
刊名	ONCOTARGET
	2014
卷号	5 期号:11 页码:3526-3540
关键词	Bladder cancer 4-aminobiphenyl Acrolein DNA repair Mutagenesis
ISSN号	1949-2553
中文摘要	Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.
WOS记录号	WOS:000339054500010
公开日期	2015-03-24
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/9308]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Lee, Hyun-Wook,Wang, Hsiang-Tsui,Weng, Mao-wen,et al. Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells[J]. ONCOTARGET,2014,5(11):3526-3540.
APA	Lee, Hyun-Wook.,Wang, Hsiang-Tsui.,Weng, Mao-wen.,Hu, Yu.,Chen, Wei-sheng.,...&Tang, Moon-shong.(2014).Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells.ONCOTARGET,5(11),3526-3540.
MLA	Lee, Hyun-Wook,et al."Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells".ONCOTARGET 5.11(2014):3526-3540.