This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marder, B A Articles by Morgan, W F Search for Related Content PubMed PubMed Citation Articles by Marder, B A Articles by Morgan, W F

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 November; 13(11): 6667-6677

Delayed chromosomal instability induced by DNA damage.

Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143-0750.

ABSTRACT

DNA damage induced by ionizing radiation can result in gene mutation, gene amplification, chromosome rearrangements, cellular transformation, and cell death. Although many of these changes may be induced directly by the radiation, there is accumulating evidence for delayed genomic instability following X-ray exposure. We have investigated this phenomenon by studying delayed chromosomal instability in a hamster-human hybrid cell line by means of fluorescence in situ hybridization. We examined populations of metaphase cells several generations after expanding single-cell colonies that had survived 5 or 10 Gy of X rays. Delayed chromosomal instability, manifested as multiple rearrangements of human chromosome 4 in a background of hamster chromosomes, was observed in 29% of colonies surviving 5 Gy and in 62% of colonies surviving 10 Gy. A correlation of delayed chromosomal instability with delayed reproductive cell death, manifested as reduced plating efficiency in surviving clones, suggests a role for chromosome rearrangements in cytotoxicity. There were small differences in chromosome destabilization and plating efficiencies between cells irradiated with 5 or 10 Gy of X rays after a previous exposure to 10 Gy and cells irradiated only once. Cell clones showing delayed chromosomal instability had normal frequencies of sister chromatid exchange formation, indicating that at this cytogenetic endpoint the chromosomal instability was not apparent. The types of chromosomal rearrangements observed suggest that chromosome fusion, followed by bridge breakage and refusion, contributes to the observed delayed chromosomal instability.

This article has been cited by other articles:

• Huang, L., Kim, P. M., Nickoloff, J. A., Morgan, W. F. (2007). Targeted and Nontargeted Effects of Low-Dose Ionizing Radiation on Delayed Genomic Instability in Human Cells. Cancer Res. 67: 1099-1104 [Abstract] [Full Text]  
• Kim, G. J., Fiskum, G. M., Morgan, W. F. (2006). A Role for Mitochondrial Dysfunction in Perpetuating Radiation-Induced Genomic Instability. Cancer Res. 66: 10377-10383 [Abstract] [Full Text]  
• J.Kim, G., Chandrasekaran, K., F.Morgan, W. (2006). Mitochondrial dysfunction, persistently elevated levels of reactive oxygen species and radiation-induced genomic instability: a review. Mutagenesis 21: 361-367 [Abstract] [Full Text]  
• Durant, S. T., Paffett, K. S., Shrivastav, M., Timmins, G. S., Morgan, W. F., Nickoloff, J. A. (2006). UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells.. Mol. Cell. Biol. 26: 6047-6055 [Abstract] [Full Text]  
• Morgan, W. F., Sowa, M. B. (2005). Effects of ionizing radiation in nonirradiated cells. Proc. Natl. Acad. Sci. USA 102: 14127-14128 [Full Text]  
• Breger, K. S., Smith, L., Thayer, M. J. (2005). Engineering translocations with delayed replication: evidence for cis control of chromosome replication timing. Hum Mol Genet 14: 2813-2827 [Abstract] [Full Text]  
• Breger, K. S., Smith, L., Turker, M. S., Thayer, M. J. (2004). Ionizing Radiation Induces Frequent Translocations with Delayed Replication and Condensation. Cancer Res. 64: 8231-8238 [Abstract] [Full Text]  
• Chen, A. Y., Shih, S.-J., Hsiao, M., Rothenberg, M. L., Prudhomme, M. (2004). Induction of Radiosensitization by Indolocarbazole Derivatives: The Role of DNA Topoisomerase I. Mol. Pharmacol. 66: 553-560 [Abstract] [Full Text]  
• Krishnaja, A.P., Sharma, N.K. (2004). Transmission of {gamma}-ray-induced unstable chromosomal aberrations through successive mitotic divisions in human lymphocytes in vitro. Mutagenesis 19: 299-305 [Abstract] [Full Text]  
• Huang, L., Grim, S., Smith, L. E., Kim, P. M., Nickoloff, J. A., Goloubeva, O. G., Morgan, W. F. (2004). Ionizing Radiation Induces Delayed Hyperrecombination in Mammalian Cells. Mol. Cell. Biol. 24: 5060-5068 [Abstract] [Full Text]  
• Ismail, S. M., Puppi, M., Prithivirajsingh, S., Munshi, A., Raju, U., Meyn, R. E., Buchholz, T. A., Story, M. D., Brock, W. A., Milas, L., Thames, H. D., Stevens, C. W. (2004). Predicting Radiosensitivity Using DNA End-Binding Complex Analysis. Clin. Cancer Res. 10: 1226-1234 [Abstract] [Full Text]  
• Okuno, Y., Hahn, P. J., Gilbert, D. M. (2004). Structure of a palindromic amplicon junction implicates microhomology-mediated end joining as a mechanism of sister chromatid fusion during gene amplification. Nucleic Acids Res 32: 749-756 [Abstract] [Full Text]  
• Wright, E. G (2004). Commentary on radiation-induced bystander effects. Hum Exp Toxicol 23: 91-94 [Abstract]  
• Nagar, S., Smith, L. E., Morgan, W. F. (2003). Mechanisms of cell death associated with death-inducing factors from genomically unstable cell lines. Mutagenesis 18: 549-560 [Abstract] [Full Text]  
• Limoli, C. L., Giedzinski, E., Morgan, W. F., Swarts, S. G., Jones, G. D. D., Hyun, W. (2003). Persistent Oxidative Stress in Chromosomally Unstable Cells. Cancer Res. 63: 3107-3111 [Abstract] [Full Text]  
• Uma Devi, P (2003). Radiosensitivity of the developing haemopoietic system in mammals and its adult consequences: animal studies. Br. J. Radiol. 76: 366-372 [Abstract] [Full Text]  
• Suzuki, K., Yokoyama, S., Waseda, S., Kodama, S., Watanabe, M. (2003). Delayed Reactivation of p53 in the Progeny of Cells Surviving Ionizing Radiation. Cancer Res. 63: 936-941 [Abstract] [Full Text]  
• Nagar, S., Smith, L. E., Morgan, W. F. (2003). Characterization of a Novel Epigenetic Effect of Ionizing Radiation: The Death-Inducing Effect. Cancer Res. 63: 324-328 [Abstract] [Full Text]  
• Rubin, H., Anderson, G. R. (2002). Correspondence re: G. Anderson et al., Intrachromosomal Genomic Instability in Human Sporadic Colorectal Cancer Measured by Genome-Wide Allelotyping and Inter-(Simple Sequence Repeat) PCR. Cancer Res., 61: 8274-8283, 2001.. Cancer Res. 62: 6350-6351 [Full Text]  
• Wang, P., Lee, J. W., Yu, Y., Turner, K., Zou, Y., Jackson-Cook, C. K., Povirk, L. F. (2002). Gene rearrangements induced by the DNA double-strand cleaving agent neocarzinostatin: conservative non-homologous reciprocal exchanges in an otherwise stable genome. Nucleic Acids Res 30: 2639-2646 [Abstract] [Full Text]  
• Li, C.-Y., Little, J. B., Hu, K., Zhang, W., Zhang, L., Dewhirst, M. W., Huang, Q. (2001). Persistent Genetic Instability in Cancer Cells Induced by Non-DNA-damaging Stress Exposures. Cancer Res. 61: 428-432 [Abstract] [Full Text]  
• Little, J. B. (2000). Radiation carcinogenesis. Carcinogenesis 21: 397-404 [Abstract] [Full Text]  
• Grosovsky, A. J. (1999). Radiation-induced mutations in unirradiated DNA. Proc. Natl. Acad. Sci. USA 96: 5346-5347 [Full Text]  
• Lehane, M. M., Bryant, P. E., Riches, A. C., Allen, L. A., Briscoe, C. V., Melville, J., Mill, A. J. (1999). 238Pu {alpha}-particle-induced C3H10T˝ transformants are less tumorigenic than the X-ray-induced equivalent. Carcinogenesis 20: 35-40 [Abstract] [Full Text]  
• Lorimore, S. A., Kadhim, M. A., Pocock, D. A., Papworth, D., Stevens, D. L., Goodhead, D. T., Wright, E. G. (1998). Chromosomal instability in the descendants of unirradiated surviving cells after alpha -particle irradiation. Proc. Natl. Acad. Sci. USA 95: 5730-5733 [Abstract] [Full Text]  
• Paulson, T. G., Almasan, A., Brody, L. L., Wahl, G. M. (1998). Gene Amplification in a p53-Deficient Cell Line Requires Cell Cycle Progression under Conditions That Generate DNA Breakage. Mol. Cell. Biol. 18: 3089-3100 [Abstract] [Full Text]  
• Little, J. B. (1997). What are the risks of low-level exposure to alpha  radiation from radon?. Proc. Natl. Acad. Sci. USA 94: 5996-5997 [Full Text]  
• King, J. S., Fairley, C. F., Morgan, W. F. (1996). DNA End Joining by the Klenow Fragment of DNA Polymerase I. J. Biol. Chem. 271: 20450-20457 [Abstract] [Full Text]  
• Di Leonardo, A, Linke, S P, Clarkin, K, Wahl, G M (1994). DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts.. Genes Dev. 8: 2540-2551 [Abstract]