Genetic and Epigenetic Features in Radiation Sensitivity Part I: Cell Signalling in Radiation Response

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2005 Jan 20

PMID 15657757

Citations 12

Authors

Michel H Bourguignon

Pablo A Gisone

Maria R Perez

Severino Michelin

Diana Dubner

Marina Di Giorgio

Edgardo D Carosella

Affiliations

Soon will be listed here.

Abstract

Recent progress especially in the field of gene identification and expression has attracted greater attention to genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. It has been proposed that the occurrence and severity of the adverse reactions to radiation therapy are also influenced by such genetic susceptibility. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation offering a better likelihood of cure for malignant tumours. This paper, the first of two parts, reviews the main mechanisms involved in cell response to ionising radiation. DNA repair machinery and cell signalling pathways are considered and their role in radiosensitivity is analysed. The implication of non-targeted and delayed effects in radiosensitivity is also discussed.

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References

Christmann M, Tomicic M, Roos W, Kaina B . Mechanisms of human DNA repair: an update. Toxicology. 2003; 193(1-2):3-34. DOI: 10.1016/s0300-483x(03)00287-7. View

Mackay R, Niemierko A, Goitein M, Hendry J . Potential clinical impact of normal-tissue intrinsic radiosensitivity testing. Radiother Oncol. 1998; 46(2):215-6. DOI: 10.1016/s0167-8140(97)00179-5. View

Komuro Y, Watanabe T, Hosoi Y, Matsumoto Y, Nakagawa K, Saito S . Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku70 expression. J Exp Clin Cancer Res. 2003; 22(2):223-8. View

Budworth H, Dianova I, Podust V, Dianov G . Repair of clustered DNA lesions. Sequence-specific inhibition of long-patch base excision repair be 8-oxoguanine. J Biol Chem. 2002; 277(24):21300-5. DOI: 10.1074/jbc.M201918200. View

Griffiths D, Barbet N, Mccready S, Lehmann A, Carr A . Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins. EMBO J. 1995; 14(23):5812-23. PMC: 394699. DOI: 10.1002/j.1460-2075.1995.tb00269.x. View

Brunner T, Gupta A, Shi Y, Hahn S, Muschel R, McKenna W . Farnesyltransferase inhibitors as radiation sensitizers. Int J Radiat Biol. 2003; 79(7):569-76. DOI: 10.1080/09553000310001610196. View

Lukas C, Bartkova J, Latella L, Falck J, Mailand N, Schroeder T . DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology. Cancer Res. 2001; 61(13):4990-3. View

BRAUNSCHWEIGER P, Basrur V, Santos O, Adessa A, Houdek P, Markoe A . Radioresistance in murine solid tumors induced by interleukin-1. Radiat Res. 1996; 145(2):150-6. View

Geara F, Peters L, Ang K, Garden A, Tucker S, Levy L . Comparison between normal tissue reactions and local tumor control in head and neck cancer patients treated by definitive radiotherapy. Int J Radiat Oncol Biol Phys. 1996; 35(3):455-62. DOI: 10.1016/s0360-3016(96)80006-x. View

10.

Turesson I, Nyman J, Holmberg E, Oden A . Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys. 1996; 36(5):1065-75. DOI: 10.1016/s0360-3016(96)00426-9. View

11.

Friedlander R, Gagliardini V, Rotello R, Yuan J . Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis. J Exp Med. 1996; 184(2):717-24. PMC: 2192702. DOI: 10.1084/jem.184.2.717. View

12.

Clutton S, Townsend K, Walker C, Ansell J, Wright E . Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures. Carcinogenesis. 1996; 17(8):1633-9. DOI: 10.1093/carcin/17.8.1633. View

13.

Morgan W, Day J, Kaplan M, McGhee E, Limoli C . Genomic instability induced by ionizing radiation. Radiat Res. 1996; 146(3):247-58. View

14.

McKenna W, Muschel R, Gupta A, Hahn S, Bernhard E . The RAS signal transduction pathway and its role in radiation sensitivity. Oncogene. 2003; 22(37):5866-75. DOI: 10.1038/sj.onc.1206699. View

15.

Thannickal V, Fanburg B . Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000; 279(6):L1005-28. DOI: 10.1152/ajplung.2000.279.6.L1005. View

16.

Neta R, Perlstein R, Vogel S, Ledney G, Abrams J . Role of interleukin 6 (IL-6) in protection from lethal irradiation and in endocrine responses to IL-1 and tumor necrosis factor. J Exp Med. 1992; 175(3):689-94. PMC: 2119144. DOI: 10.1084/jem.175.3.689. View

17.

Shao C, Stewart V, Folkard M, Michael B, Prise K . Nitric oxide-mediated signaling in the bystander response of individually targeted glioma cells. Cancer Res. 2003; 63(23):8437-42. View

18.

Sklar M . The ras oncogenes increase the intrinsic resistance of NIH 3T3 cells to ionizing radiation. Science. 1988; 239(4840):645-7. DOI: 10.1126/science.3277276. View

19.

Morgan W . Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?. Oncogene. 2003; 22(45):7094-9. DOI: 10.1038/sj.onc.1206992. View

20.

Jeggo P, Taccioli G, Jackson S . Menage à trois: double strand break repair, V(D)J recombination and DNA-PK. Bioessays. 1995; 17(11):949-57. DOI: 10.1002/bies.950171108. View