TY - JOUR
T1 - 8-Hydroxydeoxyguanosine causes death of human leukemia cells deficient in 8-oxoguanine glycosylase 1 activity by inducing apoptosis
AU - Hyun, Jin Won
AU - Jung, Yoon Chul
AU - Kim, Hyun Sook
AU - Choi, Eun Young
AU - Kim, Ja Eun
AU - Yoon, Byung Hak
AU - Yoon, Sun Hee
AU - Lee, Yun Sil
AU - Choi, Jinhee
AU - You, Ho Jin
AU - Chung, Myung Hee
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Our previous study showed that KG-1, a human acute leukemia cell line, has mutational loss of 8-oxoguanine (8-hydroxyguanine; oh8Gua) glycosylase 1 (OGG1) activity and that its viability is severely affected by 8-hydroxydeoxyguanosine (8-oxodeoxyguanosine; oh8dG). In the present study, the nature of the killing action of oh8dG on KG-1 was investigated. Signs observed in oh8dG-treated KG-1 cells indicated that death was due to apoptosis, as demonstrated by: increased sub-G1 hypodiploid (apoptotic) cells, DNA fragmentation, and apoptotic body formation; loss of mitochondrial transmembrane potential, the release of cytochrome c from mitochondria into the cytosol, and the down-regulation of bcl-2; and the activation of caspases 8, 9, and 3, and the efficient inhibition of the apoptotic process by caspases inhibitors. This apoptosis appears not to be associated with Fas/Fas ligand because the expressions of these proteins were unchanged. Apoptotic KG-1 cells showed a high concentration of oh8Gua in DNA. Moreover, the increased concentration of oh8Gua in DNA, and the apoptotic process were not suppressed by the antioxidant, N-acetylcysteine, and thus the process is independent of reactive oxygen species. Of the 18 cancer cell lines treated with oh8dG, 3 cell lines (H9, CEM-CM3, and Molt-4) were found to be committed to apoptosis, and all of these showed very low OGG1 activity and a marked increase in the concentration of oh8Gua in DNA. These observations indicate that in addition to its mutagenic action, oh8Gua in DNA disturbs cell viability by inducing apoptosis.
AB - Our previous study showed that KG-1, a human acute leukemia cell line, has mutational loss of 8-oxoguanine (8-hydroxyguanine; oh8Gua) glycosylase 1 (OGG1) activity and that its viability is severely affected by 8-hydroxydeoxyguanosine (8-oxodeoxyguanosine; oh8dG). In the present study, the nature of the killing action of oh8dG on KG-1 was investigated. Signs observed in oh8dG-treated KG-1 cells indicated that death was due to apoptosis, as demonstrated by: increased sub-G1 hypodiploid (apoptotic) cells, DNA fragmentation, and apoptotic body formation; loss of mitochondrial transmembrane potential, the release of cytochrome c from mitochondria into the cytosol, and the down-regulation of bcl-2; and the activation of caspases 8, 9, and 3, and the efficient inhibition of the apoptotic process by caspases inhibitors. This apoptosis appears not to be associated with Fas/Fas ligand because the expressions of these proteins were unchanged. Apoptotic KG-1 cells showed a high concentration of oh8Gua in DNA. Moreover, the increased concentration of oh8Gua in DNA, and the apoptotic process were not suppressed by the antioxidant, N-acetylcysteine, and thus the process is independent of reactive oxygen species. Of the 18 cancer cell lines treated with oh8dG, 3 cell lines (H9, CEM-CM3, and Molt-4) were found to be committed to apoptosis, and all of these showed very low OGG1 activity and a marked increase in the concentration of oh8Gua in DNA. These observations indicate that in addition to its mutagenic action, oh8Gua in DNA disturbs cell viability by inducing apoptosis.
UR - http://www.scopus.com/inward/record.url?scp=12244270357&partnerID=8YFLogxK
M3 - Article
C2 - 12612057
AN - SCOPUS:12244270357
SN - 1541-7786
VL - 1
SP - 290
EP - 299
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 4
ER -
