Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aburatani H, Hippo Y, Ishida T, Tahashima R, Matsuba C, Kodama T, Takao M, Yasui A, Yamamoto K, Asano M, Fukasawa K, Yoshinari T, Inoue H, Ohtsuka E and Nishimura S. . 1997 Cancer Res. 57: 2151–2156.
Arai K, Morishita K, Shinmura K, Kohno T, Kim SR, Nohmi T, Taniwaki M, Ohwada S and Yokoda J. . 1997 Oncogene 14: 2857–2861.
Auffret Van Der Kemo P, Thomas D, Barbey R, Oliveira R and Boiteux S. . 1996 Proc. Natl. Sci. USA 93: 5197–5202.
Bruner SD, Norman DPG and Verdin GL. . 2000 Nature 403: 859–866.
Calabresi P and Chabner BA. . 1991 In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics: Antineoplastic Agents. Gilman GA, Rall TW, Nies AS and Taylor P. (eds). Pergamon Press: New York, pp. 1227–1236.
Carmichael J, DeGraff WG and Gazdar AF. . 1987 Cancer Res. 47: 936–941.
Chevillard S, Radicella JO, Levalois C, Lebeau J, Poupon MF, Oudard S, Dutrillaux B and Boiteux S. . 1998 Oncogene 16: 3083–3086.
Choi JY, Kim HS, Kang HK, Lee DW, Choi EM and Chung MY. . 1999 Free Radical Biol. Med. 27: 848–854.
Chung MH, Kasai H, Jones DS, Inoue H, Ishikawa H, Ohtsuka E and Nishimura S. . 1991a Mutation Res. 254: 1–12.
Chung MH, Kim HS, Ohtsuka E, Kasai H, Yamamoto F and Nishimura S. . 1991b Biochem. Biophys. Res. Commun. 178: 1472–1478.
Dherin C, Radicella JP, Dizdaroglu M and Boiteux S. . 1999 Nucleic Acids Res. 27: 4001–4007.
Hayakawa H, Taketomi A, Sakumi K, Kuwano M and Sekiguchi M. . 1995 Biochemistry 34: 89–95.
Kasai H, Crain PF, Kuchino Y, Nishimura S, Ootsuyama A and Tanooka H . 1986 Carcinogenesis 7: 1849–1851.
Kim HS, Park YW, Kasai H, Nishimura S, Park CW, Choi KH and Chung MH. . 1996 Mutation Res. 363: 115–124.
Kohno T, Shinmura K, Tosaka M, Tani M, Kim SR, Sugimura H, Nohmi T, Kasai H and Yokota J. . 1998 Oncogene 16: 3219–3225.
Lee YS, Lee HS, Park MK, Hwang ES, Park EM, Kasai H and Chung MH. . 1993 Biochem. Biophys. Res. Commun. 196: 1545–1551.
Lu R, Nash HM and Verdine GL. . 1997 Curr. Biol. 7: 397–407.
Nash HM, Bruner SD, Scharer OD, Kawate T, Addona TA, Spooner E, Lane WS and Verdine G. . 1996 Curr. Biol. 6: 968–980.
Radicella JP, Dherin C, Desmaze C, Fox MS and Boiteux S. . 1997 Proc. Natl. Sci. USA 94: 8010–8015.
Roldan-Arjona T, Wei YF, Carter KC, Klungland A, Anselmino C, Wang RP, Augustus M and Lindahl T. . 1997 Proc. Natl. Sci. USA 94: 8016–8020.
Shinmura K, Kohno T, Kasai H, Koda K, Sugimura H and Yokota J. . 1998 Jpn. J. Cancer Res. 89: 825–828.
Smith PK, Krohn RI, Hermanson GT, Mallia AK, Goeke NM, Olson BJ and Klenk DC. . 1985 Anal. Biochem. 150: 76–85.
Tchou J, Kasai H, Shibutani S, Chung MH and Laval J. . 1991 Proc. Natl. Acad. Sci. USA 88: 4690–4694.
Tu CP and Cohen SN. . 1980 Gene 10: 177–183.
Yamamoto F, Chung MH, Kasai H, Ohtsuka E, Hori T and Nishimura S. . 1992 Jpn. J. Cancer Res. 83: 351–357.
Acknowledgements
This study was supported in part by a grant for Radiation Research from the Ministry of Science and Technology of Korea.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hyun, JW., Choi, JY., Zeng, HH. et al. Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1. Oncogene 19, 4476–4479 (2000). https://doi.org/10.1038/sj.onc.1203787
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203787
Keywords
This article is cited by
-
ROS production by mitochondria: function or dysfunction?
Oncogene (2024)
-
Baicalein (5,6,7-trihydroxyflavone) reduces oxidative stress-induced DNA damage by upregulating the DNA repair system
Cell Biology and Toxicology (2012)
-
OGG1 is a novel prognostic indicator in acute myeloid leukaemia
Oncogene (2010)
-
8-Hydroxydeoxyguanosine induces senescence-like changes in KG-1, human acute myelocytic leukemia cell line
Biotechnology and Bioprocess Engineering (2007)
-
Targeting of mutant hogg1in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress
BMC Cancer (2006)