Radiation sensitivity depends on OGG1 activity status in human leukemia cell lines.
To assess the role of 8-oxoguanine glycosylase (OGG1) in the cell defense against radiation injury, the radiation-induced cytotoxicities were compared between the mutant type KG-1 featuring a loss of OGG1 activity due to a homozygous mutation of Arg 229 Gln, and the wild type U937. While the following three obvious toxicities were displayed in KG-1, they were observed only minimally in U937. These were: a dramatic arrest at the G2/M phase indicated by a marked increase in both the number of G2/M cells and the expression of cyclin B1, cdc2, and mitotic phosphoprotein monoclonal-2 (MPM-2)-reactive proteins; a severe apoptosis shown by a marked increase in the number of cells with hypo-diploid DNA and DNA fragmentation; and as a result, a severe inhibition of cell growth and proliferation measured by the MTT test and [(3)H]-thymidine uptake assay. As expected, KG-1 exhibited a significant increase in the 8-hydroxyguanine level in DNA whereas U937 did not. However, the level of irradiation-induced lipid peroxidation was almost the same in both cell lines. All of these symptoms shown by KG-1 were observed in Molt-4 and CEM-CM3, which were also found to feature low OGG1 activity. These findings suggest that OGG1 plays an important role in cell survival from radiation-induced damage and are also indicative of the capability of 8-hydroxyguanine in DNA to induce cellular toxicities.
Hyun
Jin-Won
JW
Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea.
Cheon
Gi-Jeong
GJ
Kim
Hyun-Sook
HS
Lee
Yun-Sil
YS
Choi
Eun-Young
EY
Yoon
Byung-Hak
BH
Kim
Jeong-Soon
JS
Chung
Myung-Hee
MH
D017209:Apoptosis / Q000528:radiation effects; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004249:DNA Damage / Q000528:radiation effects; D043382:DNA-Formamidopyrimidine Glycosylase; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000201:enzymology* / Q000235:genetics; D015227:Lipid Peroxidation / Q000528:radiation effects; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011836:Radiation Tolerance; D013997:Time Factors; D014407:Tumor Cells, Cultured
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase