Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1.
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. Oncogene (2000) 19, 4476 - 4479.
Hyun
J W
JW
Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
Choi
J Y
JY
Zeng
H H
HH
Lee
Y S
YS
Kim
H S
HS
Yoon
S H
SH
Chung
M H
MH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics*; D009699:N-Glycosyl Hydrolases / Q000187:drug effects / Q000235:genetics*; D017354:Point Mutation; D014407:Tumor Cells, Cultured
D000080242:8-Hydroxy-2'-Deoxyguanosine; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine