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Molecular and Cellular Biology, June 2004, p. 5060-5068, Vol. 24, No. 11
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.11.5060-5068.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Ionizing Radiation Induces Delayed Hyperrecombination in Mammalian Cells

Lei Huang,^1,2* Suzanne Grim,² Leslie E. Smith,² Perry M. Kim,³ Jac A. Nickoloff,⁴ Olga G. Goloubeva,⁵ and William F. Morgan^2,6

Graduate Program in Human Genetics,¹ Radiation Oncology Research Laboratory,² Biostatistics Division,⁵ Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201-1559,⁶ Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6,³ Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131⁴

Received 20 October 2003/ Returned for modification 4 December 2003/ Accepted 9 March 2004

Exposure to ionizing radiation can result in delayed effects that can be detected in the progeny of an irradiated cell multiple generations after the initial exposure. These effects are described under the rubric of radiation-induced genomic instability and encompass multiple genotoxic endpoints. We have developed a green fluorescence protein (GFP)-based assay and demonstrated that ionizing radiation induces genomic instability in human RKO-derived cells and in human hamster hybrid GM10115 cells, manifested as increased homologous recombination (HR). Up to 10% of cells cultured after irradiation produce mixed GFP^+/– colonies indicative of delayed HR or, in the case of RKO-derived cells, mutation and deletion. Consistent with prior studies, delayed chromosomal instability correlated with delayed reproductive cell death. In contrast, cells displaying delayed HR showed no evidence of delayed reproductive cell death, and there was no correlation between delayed chromosomal instability and delayed HR, indicating that these forms of genome instability arise by distinct mechanisms. Because delayed hyperrecombination can be induced at doses of ionizing radiation that are not associated with significantly reduced cell viability, these data may have important implications for assessment of radiation risk and understanding the mechanisms of radiation carcinogenesis.

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* Corresponding author. Mailing address: Radiation Oncology Research Laboratory, Bressler Research Building, Room 7-002, University of Maryland, 655 W. Baltimore St., Baltimore, MD 21201-1559. Phone: (410) 706-1572. Fax: (410) 706-6138. E-mail: lhuan001{at}umaryland.edu.

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Molecular and Cellular Biology, June 2004, p. 5060-5068, Vol. 24, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.11.5060-5068.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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]  
• 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]