Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1

被引:53
作者
Hyun, JW
Choi, JY
Zeng, HH
Lee, YS
Kim, HS
Yoon, SH
Chung, MH
机构
[1] Seoul Natl Univ, Coll Med, Dept Pharmacol, Chongno Gu, Seoul 110744, South Korea
[2] Beijing Med Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
[3] Korea Canc Ctr Hosp, Lab Radiat Effect, Nowon Gu, Seoul 139706, South Korea
关键词
KG-1; 8-hydroxyguanine; hOGG1; mutation; cytotoxicity;
D O I
10.1038/sj.onc.1203787
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We tested the cytotoxic action of 8-hydroxyguanine (8ohG) by observing the viability of several leukemic cell lines (KG-1, U937, Jurkat and K 562) in the presence of 8-hydroxydeoxyguanosine (8ohdG), a nucleoside of 8ohG, It was found that 8ohdG showed cytotoxic action only to KG-1 and that only KG-1 showed a homozygous arginine 209 to glutamine mutation in the hOGG1 gene with an almost negligible hOGG1 enzyme activity, Possibly, the selective cytotoxicity in 8ohdG to KG-1 may be due to its low capacity to cope with an increase in the 8ohG level in DNA resulting from the incorporation of 8ohdG present in the culture media. The mutational impairment of hOGG1 in KG-1 is the first report in leukemic cell lines. Using KG-1 with impaired hOGG1, we demonstrated cytotoxicity of 8ohdG probably due to its incorporation into cellular DNA. This new property of KG-1 may allow it to serve as an useful tool for studies of OGG1, oxidative DNA damage and the cytotoxic action of 8ohG.
引用
收藏
页码:4476 / 4479
页数:4
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