Protection of Tissue-culture Cells against Ionizing Radiation

Vos, O.; Budke, L.; Vergroesen, A.J.

doi:10.1080/09553006214551191

Cited by 41 publications

References 16 publications

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Radiosensitizers and Radioprotective Agents

Bump¹,

Hoffman²,

Foye

2003

Burger's Medicinal Chemistry and Drug Discovery

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Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. An important potential use for these agents is to modify the outcome of radiation therapy. Potential radioprotectors or radiosensitizers are organized in this review according to mechanism of action. Most of the agents studied are believed to act by reacting with DNA radicals that are produced within milliseconds of exposure to ionizing radiation. According to this mechanism, protectors restore a single electron to electron‐deficient radicals, preventing degradation of the structure of DNA, whereas sensitizers, such as molecular oxygen or nitroimidazoles, form adducts with these radicals, resulting in damage fixation. WR2721 (Ethyol) is the best‐characterized chemical radioprotector. Preferential activation of WR2721 in certain normal tissues by removal of a phosphate group provides a rationale for selective protection of these tissues. Cytokines and biological modifiers represent an important emerging class of radioprotectors that may be particularly useful in modifying bone marrow injury. Nitroimidazoles have been the most widely studied chemical radiosensitizers. Although clinical results with nitroimidazoles have not been impressive, the potential for this approach has not been fully explored, given that the doses that can be administered have been limited by drug toxicity and supplemental strategies, such as concurrent depletion of endogenous protectors, have not been explored in the clinic. Modifiers of tumor oxygenation represent an important class of radiosensitizers that are currently generating considerable clinical interest. RSR13, a modifier of the oxygen affinity of hemoglobin, is highlighted as an example of the process of drug development for this type of agent.

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Radiosensitizers and Radioprotective Agents

Bump¹,

Hoffman²,

Foye

2003

Burger's Medicinal Chemistry and Drug Discovery

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Effects of Ionizing Radiation on Mammalian Cells

Little

Williams

1977

Comprehensive Physiology

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The sections in this article are: Physical and Chemical Events Development of Radiation Injury The Target Theory Direct and Indirect Effects, Radiation Chemistry Effects on Cell Division Division Delay Mitotic Inhibition (Reproductive Failure) Radiation Sensitivity in Different Phases of the Life Cycle Chromosomal Damage Interphase Death Nonlethal Heritable Changes Biological Variation in Radiation Sensitivity Mechanisms Modification of Radiation Effects Physical Factors Chemical Radiation Protection and Sensitization Oxygen Effect Intracellular Recovery Processes Repair of Potentially Lethal Damage Repair of Sublethal Damage (Split‐Dose Recovery) Molecular Repair Processes Damage Observed in DNA Cellular Repair Systems for DNA Damage Repair Activities in Mammalian Cells Correlation of DNA Repair with Biological Effects Concluding Remarks Addendum

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