Potassium bromate treatment predominantly causes large deletions, but not GC > TA transversion in human cells

doi:10.1016/j.mrfmmm.2007.02.029

	Potassium bromate treatment predominantly causes large deletions, but not GC > TA transversion in human cells
	Luan, Yang ; Suzuki, Takayoshi ; Palanisamy, Rajaguru ; Takashima, Yoshio ; Sakamoto, Hiroko ; Sakuraba, Mayumi ; Koizumi, Tomoko ; Saito, Mika ; Matsufuji, Hiroshi ; Yamagatae, Kazuo
刊名	MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
	2007-06-01
卷号	619 期号:1-2 页码:113-123
关键词	potassium brornate (KBrO3) TK-mutation loss of heterozygosity (LOH) 8-hydroxydeoxy,guanosine (8OHdG) gene expression profile
ISSN号	0027-5107
DOI	10.1016/j.mrfmmm.2007.02.029
文献子类	Article
英文摘要	Potassium bromate (KBrO3) is strongly carcinogenic in rodents and mutagenic in bacteria and mammalian cells in vitro. The proposed genotoxic mechanism for KBrO3 is oxidative DNA damage. KBrO3 can generate high yields of 8-hydroxydeoxyguanosine (8OHdG) DNA adducts, which cause GC > TA transversions in cell-free systems. In this study, we investigated the in vitro genotoxicity of KBrO3 in human lymphoblastoid TK6 cells using the comet (COM) assay, the micronucleus (MN) test, and the thymidine kinase (TK) gene mutation assay. After a 4 h treatment, the alkaline and neutral COM assay demonstrated that KBrO3 directly yielded DNA damages including DNA double strand breaks (DSBs). KBrO3 also induced MN and TK mutations concentration-dependently. At the highest concentration (5 mM), KBrO3 induced MN and TK mutation frequencies that were over 30 times the background level. Molecular analysis revealed that 90% of the induced mutations were large deletions that involved loss of heterozygosity (LOH) at the TK locus. Ionizing-irradiation exhibited similar mutational spectrum in our system. These results indicate that the major genotoxicity of KBrO3 may be due to DSBs that lead to large deletions rather than to 8OHdG adducts that lead to GC > TA transversions, as is commonly believed. To better understand the genotoxic mechanism of KBrO3, we analyzed gene expression profiles of TK6 cells using Affymetrix Genechip. Some genes involved in stress, apoptosis, and DNA repair were up-regulated by the treatment of KBrO3. However, we could not observe the similarity of gene expression profile in the treatment of KBrO3 to ionizing-irradiation as well as oxidative damage inducers. (c) 2007 Elsevier B.V. All rights reserved.
WOS关键词	OXIDATIVE DNA-DAMAGE ; HUMAN-LYMPHOBLASTOID-CELLS ; BASE EXCISION-REPAIR ; IONIZING-RADIATION ; TK6 CELLS ; MUTAGENIC RESPONSES ; RENAL CARCINOGEN ; FOOD-ADDITIVES ; COMET ASSAY ; V79 CELLS
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000246667800012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273251]
专题	中国科学院上海药物研究所
通讯作者	Honma, Masamitsu
作者单位	1.Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 1588501, Japan 2.Natl Inst Hlth Sci, Div Cellular & Gene Therapy Prod, Setagaya Ku, Tokyo 1588501, Japan 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat, Shanghai 200031, Peoples R China 4.Bharathidasan Univ, Dept Biotechnol, Sch Engn & Technol, Tiruchchirappalli 620024, India 5.Nihon Univ, Coll Bioresource Sci, Dept Food Sci & Technol, Fujisawa, Kanagawa 2528510, Japan
推荐引用方式 GB/T 7714	Luan, Yang,Suzuki, Takayoshi,Palanisamy, Rajaguru,et al. Potassium bromate treatment predominantly causes large deletions, but not GC > TA transversion in human cells[J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,2007,619(1-2):113-123.
APA	Luan, Yang.,Suzuki, Takayoshi.,Palanisamy, Rajaguru.,Takashima, Yoshio.,Sakamoto, Hiroko.,...&Honma, Masamitsu.(2007).Potassium bromate treatment predominantly causes large deletions, but not GC > TA transversion in human cells.MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS,619(1-2),113-123.
MLA	Luan, Yang,et al."Potassium bromate treatment predominantly causes large deletions, but not GC > TA transversion in human cells".MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS 619.1-2(2007):113-123.