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Gamma-Irradiation and Doxorubicin Treatment of Normal Human Cells Cause Cell Cycle Arrest Via Different Pathways  

Lee, Seong Min (School of Life Sciences and Biotechnology, Korea University)
Youn, BuHyun (School of Molecular Biosciences, Washington State University)
Kim, Cha Soon (School of Life Sciences and Biotechnology, Korea University)
Kim, Chong Soon (Radiation and Health Research Institute)
Kang, ChulHee (School of Molecular Biosciences, Washington State University)
Kim, Joon (School of Life Sciences and Biotechnology, Korea University)
Publication Information
Molecules and Cells / v.20, no.3, 2005 , pp. 331-338 More about this Journal
Abstract
Ionizing radiation and doxorubicin both produce oxidative damage and double-strand breaks in DNA. Double-strand breaks and oxidative damage are highly toxic and cause cell cycle arrest, provoking DNA repair and apoptosis in cancer cell lines. To investigate the response of normal human cells to agents causing oxidative damage, we monitored alterations in gene expression in F65 normal human fibroblasts. Treatment with ${\gamma}$-irradiation and doxorubicin altered the expression of 23 and 68 known genes, respectively, with no genes in common. Both agents altered the expression of genes involved in cell cycle arrest, and arrested the treated cells in $G_2M$ phase 12 h after treatment. 24 h after ${\gamma}$-irradiation, the percentage of $G_1$ cells increased, whereas after doxorubicin treatment the percentage of $G_2M$ cells remained constant for 24 h. Our results suggest that F65 cells respond differently to ${\gamma}$-irradiation- and doxorubicin-induced DNA damage, probably using entirely different biochemical pathways.
Keywords
${\gamma}$-Irradiation; Differential Gene Expression; Doxorubicin; Normal Human Fibroblasts;
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Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 12  (Related Records In Web of Science)
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1 Aly, M. S., Othman, O. E., and El Nahas, S. M. (1999) Specific numerical chromosomal aberrations induced by adriamycin. Environ. Mol. Mutagen. 33, 161-166   DOI   ScienceOn
2 Backlund, M. G., Trasti, S. L., Backlund, D. C., Cressman, V. L., Godfrey, V., et al. (2001) Impact of ionizing radiation and genetic background on mammary tumorigenesis in p53- deficient mice. Cancer Res. 61, 6577-6582
3 Chen, Y. W., Zhao, P., Borup, R., and Hoffman, E. P. (2000) Expression profiling in the muscular dystrophies: identification of novel aspects of molecular pathophysiology. J. Cell Biol. 151, 1321?1336   DOI
4 Janicke, R. U., Engels, I. H., Dunkern, T., Kaina, B., Schulze- Osthoff, K., et al. (2001) Ionizing radiation but not anticancer drugs causes cell cycle arrest and failure to activate the mitochondrial death pathway in MCF-7 breast carcinoma cells. Oncogene 20, 5043-5053   DOI
5 Lakin, N. D. and Jackson, S. P. (1999) Regulation of p53 in response to DNA damage. Oncogene 18, 7644-7655   DOI
6 Qin, C. and Bruce, N. A. (1994) Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells. Proc. Natl. Acad. Sci. USA 91, 4130-4134
7 Saijo, M., Sakai, Y., Kishino, T., Niikawa, N., Matsuura, Y., et al. (1995) Molecular cloning of a human protein that binds to the retinoblastoma protein and chromosomal mapping. Genomics 27, 511-519   DOI   ScienceOn
8 Wahl, G. M. and Carr, A. M. (2001) The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat. Cell Biol. 3, E277-286   DOI   ScienceOn
9 Yamamoto, H., Flannery, M. L., Kupriyanov, S., Pearce, J., McKercher, S. R., et al. (1998) Defective trophoblast function in mice with a targeted mutation of Ets2. Genes Dev. 12, 1315-1326   DOI
10 Yamada, N. A., Parker, J. M., and Farber, R. A. (2003) Mutation frequency analysis of mononucleotide and dinucleotide repeats after oxidative stress. Environ. Mol. Mutagen. 42, 75-84   DOI   ScienceOn
11 Von Sonntag, C. (1987) The chemical basis of radiation biology, Taylor & Francis, London
12 Green, J. A., Kirwan, J. M., Tierney, J. F., Symonds, P., Fresco,L., et al. (2001) Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet 358, 781-786   DOI   ScienceOn
13 Culine, S., Kattan, J., Zanetta, S., Theodore, C., Fizazi, K., et al. (1998) Evaluation of estramustine phosphate combined with weekly doxorubicin in patients with androgen-independent prostate cancer. Am. J. Clin. Oncol. 21, 470?474   DOI   ScienceOn
14 Vairapandi, M., Balliet, A. G., Hoffman, B., and Liebermann, D. A. (2002) GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J. Cell Physiol. 192, 327-338   DOI   ScienceOn
15 Barlogie, B., Drewinko, B., Johnston, D. A., and Freireich, E. J. (1976) The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line. Cancer Res. 36, 1975-1979
16 Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., et al. (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282, 1497-1501   DOI   ScienceOn
17 Boiteux, S., Gajewski, E., Laval, J., and Dizdaroglu, M. (1992) Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry 31, 106-110   DOI   ScienceOn
18 Khanna, K. K. and Jackson, S. P. (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 27, 247-254   DOI   ScienceOn
19 Park, W. Y., Hwang, C. I., Im, C. N., Kang, M. J., Woo, J. H., et al. (2002) Identification of radiation-specific responses from gene expression profile. Oncogene 21, 8521-8528   DOI   ScienceOn
20 Bontenbal, M., Sieuwerts, A. M., Klijn, J. G., Peters, H. A., Krijnen, H. L., et al. (1989) Effect of hormonal manipulation and doxorubicin administration on cell cycle kinetics of human breast cancer cells. Br. J. Cancer 60, 688-692   DOI   ScienceOn
21 Yacoub, A., Park, J. S., Qiao, L., Dent, P., and Hagan, M. P. (2001) MAPK dependence of DNA damage repair: ionizing radiation and the induction of expression of the DNA repair genes XRCC1 and ERCC1 in DU145 human prostate carcinoma cells in a MEK1/2 dependent fashion. Int. J. Radiat. Biol. 77, 1067-1078   DOI
22 Gong, B. and Almasan, A. (2000) Apo2 ligand/TNF-related apoptosis-inducing ligand and death receptor 5 mediate the apoptotic signaling induced by ionizing radiation in leukemic cells. Cancer Res. 60, 5754-5760
23 Kasten, M. and Giordano, A. (2001) Cdk10, a Cdc2-related kinase, associates with the Ets2 transcription factor and modulates its transactivation activity. Oncogene 20, 1832-1838   DOI
24 Liu, L. F. (1989) DNA topoisomerase poisons as antitumor drugs. Annu. Rev. Biochem. 58, 351-375   DOI   ScienceOn
25 Sergere, J. C., Thuret, J. Y., Le Roux, G., Carosella, E. D., and Leteurtre, F. (2000) Human CDK10 gene isoforms. Biochem. Biophys. Res. Commun. 276, 271-277   DOI   ScienceOn
26 Brugarolas, J., Moberg, K., Boyd, S. D., Taya, Y., Jacks, T., et al. (1999) Inhibition of cyclin-dependent kinase 2 by p21 is necessary for retinoblastoma protein-mediated G1 arrest after gamma-irradiation. Proc. Natl. Acad. Sci. USA 96, 1002-1007
27 Sui, M. and Fan, W. (2005) Combination of gamma-radiation antagonizes the cytotoxic effects of vincristine and vinblastine on both mitotic arrest and apoptosis. Int. J. Radiat. Oncol. Biol. Phys. 61, 1151-1158   DOI   ScienceOn
28 Breimer, L. H. (1990) Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: the role of DNA base damage. Mol. Carcinog. 3, 188-197   DOI   ScienceOn
29 Ryu, M. R., Paik, S. Y., and Chung, S. M. (2005) Combined effect of heptaplatin and ionizing radiation on human squamous carcinoma cell lines. Mol. Cells 19, 143-148