Mutagenicity of 7-ketocholesterol in CHO cells: The role of lipid peroxidation

doi:10.1016/j.tox.2020.152587

	Mutagenicity of 7-ketocholesterol in CHO cells: The role of lipid peroxidation
	Wang, Xiaofei 1; Li, Yintao 1,2; Xia, Xuanyi 1; Zhang, Min 1; Ge, Chunmei 1; Xia, Xiaoxiao 1; Xiao, Hourong 1; Xu, Shengmin 3
刊名	TOXICOLOGY
	2020-12-15
卷号	446
关键词	7-ketocholesterol Mutagenicity DNA damage Apoptosis Lipid peroxidation
ISSN号	0300-483X
DOI	10.1016/j.tox.2020.152587
通讯作者	Xiao, Hourong(xhr@hfuu.edu.cn) ; Xu, Shengmin(shmxu@mail.ustc.edu.cn)
英文摘要	As an important cholesterol oxide, 7-ketocholesterol plays a deleterious role in the occurrence of cancer. Although the fact had been proved that 7-ketocholesterol could induce several biological phenomena, including apoptosis, DNA damage, et al., this issue whether 7-ketocholesterol led to mutagenesis in mammalian cells re-mains largely unexplored. Here, we investigated the major role of lipid peroxidation in the genotoxic response to 7-ketocholesterol in chinese hamster ovary (CHO) cells. The results showed that 7-ketocholesterol induced gene mutation and DNA double-strand breaks (DSBs) in concentrationand time-dependent manner. After CHO cells were treated with 25 mu M 7-ketocholesterol for 48 h, the mutation frequency at hprt gene loci and the level of gamma-H2AX protein were both significantly increased. Exposure to 7-ketocholesterol resulted in a concentration dependent increase in the apoptotic rate and the protein expression of cleaved caspase-3 and-7 in CHO cells. Moreover, a significant increase of superoxide dismutase (SOD) activity and content of malondialdehyde (MDA) was also observed. Using a inhibitor of lipid peroxidation (butylated hydroxytoluene), it was found to remarkably inhibit the genotoxicity and MDA levels caused by 7-ketocholesterol. These findings indicated that lipid peroxidation was involved in the mutagenic process of 7-ketocholesterol in CHO cells.
资助项目	Natural Science Foundation of Anhui Province[1808085QB37] ; Opening Foundation of Anhui Province of Key Laboratory of Environmental Toxicology and Pollution Control Technology[Y79AH72588] ; Talent Research Foundation of Hefei University[16-17RC03] ; Natural Science Foundation of China[31670860] ; Key Project of Research and Development of Anhui Province[1804a0802224] ; Project of Scientific and Technological Research of Anhui Province[1301032168] ; Major Project of Research and Development Foundation of Hefei University[19ZR13ZDA]
WOS关键词	DNA-DAMAGE ; ACID ; MALONDIALDEHYDE ; OXYSTEROLS ; APOPTOSIS ; REPAIR
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000593910100005
资助机构	Natural Science Foundation of Anhui Province ; Opening Foundation of Anhui Province of Key Laboratory of Environmental Toxicology and Pollution Control Technology ; Talent Research Foundation of Hefei University ; Natural Science Foundation of China ; Key Project of Research and Development of Anhui Province ; Project of Scientific and Technological Research of Anhui Province ; Major Project of Research and Development Foundation of Hefei University
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/105421]
专题	中国科学院合肥物质科学研究院
通讯作者	Xiao, Hourong; Xu, Shengmin
作者单位	1.Hefei Univ, Sch Biol Food & Environm, Hefei 230601, Peoples R China 2.Chinese Acad Sci, Hefei Inst Phys Sci, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, Hefei 230031, Peoples R China 3.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei 230601, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xiaofei,Li, Yintao,Xia, Xuanyi,et al. Mutagenicity of 7-ketocholesterol in CHO cells: The role of lipid peroxidation[J]. TOXICOLOGY,2020,446.
APA	Wang, Xiaofei.,Li, Yintao.,Xia, Xuanyi.,Zhang, Min.,Ge, Chunmei.,...&Xu, Shengmin.(2020).Mutagenicity of 7-ketocholesterol in CHO cells: The role of lipid peroxidation.TOXICOLOGY,446.
MLA	Wang, Xiaofei,et al."Mutagenicity of 7-ketocholesterol in CHO cells: The role of lipid peroxidation".TOXICOLOGY 446(2020).