Biological basis of radiation sensitivity. Part 2: Cellular and molecular determinants of radiosensitivity.
Recent studies have elucidated some of the molecular and cellular mechanisms that determine the sensitivity or resistance to ionizing radiation. These findings ultimately may be useful in devising new strategies to improve the therapeutic ratio in cancer treatment. Despite the rapid advances in knowledge of cellular functions that affect radiosensitivity, we still cannot account for most of the clinically observed heterogeneity of normal tissue and tumor responses to radiotherapy, nor can we accurately predict which individual tumors will be controlled locally and which patients will develop more severe normal tissue damage after radiotherapy. However, several candidate genes for which deletion or loss of function mutations may be associated with altered cellular radiosensitivity (e.g., ATM, p53, BRCA1, BRCA2, DNA-PK) have been identified. Some of the differences in normal tissue sensitivity to radiation may stem from mutations with milder effects, heterozygosity, or polymorphisms of these genes. Finally, molecular mechanisms linking genetic instability, radiosensitivity, and predisposition to cancer are being unraveled.
Rosen
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Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York, USA.
Fan
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Goldberg
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Rockwell
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D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D016207:Cytokines / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000235:genetics* / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000528:radiation effects; D016158:Genes, p53 / Q000235:genetics / Q000528:radiation effects; D020022:Genetic Predisposition to Disease; D006133:Growth Substances / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000532:radiotherapy; D009857:Oncogenes / Q000235:genetics / Q000528:radiation effects; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects
D016207:Cytokines; D004273:DNA, Neoplasm; D006133:Growth Substances