著者

Nair Cherupally K.K. Parida Dillip K. Nomura Taisei

出版者

日本放射線影響学会

雑誌

Journal of radiation research (ISSN:04493060)

巻号頁・発行日

vol.42, no.1, pp.21-37, 2001-03

被引用文献数

38 320

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Radiotherapy is the most common modality for treating human cancers. Eighty percent of cancer patients need radiotherapy at some time or other, either for curative or palliative purpose. To obtain optimum results, a judicious balance between the total dose of radiotherapy delivered and the threshold limit of the surrounding normal critical tissues is required. In order to obtain better tumor control with a higher dose, the normal tissues should be protected against radiation injury. Thus, the role of radioprotective compounds is very important in clinical radiotherapy. Ionizing radiation causes damage to living tissues through a series of molecular events, such as photoelectric, Compton and Auger effects, depending on the radiation energy. Because human tissues contain 80% water, the major radiation damage is due to the aqueous free radicals, generated by the action of radiation on water. The major free radicals resulting from aqueous radiolysis are OH, H, e_<aq>^- , HO_2, H_ 3 O^+ , etc. These free radicals react with cellular macromolecules, such as DNA, RNA, proteins, membrane, etc, and cause cell dysfunction and mortality. These reactions take place in tumor as well as normal cells when exposed to radiation. The radiation damage to a cell is potentiated or mitigated depending on several factors, such as the presence of oxygen, sulfhydryl compounds and other molecules in the cellular milieu. In the presence of oxygen, hydrated electrons and H atoms react with molecular oxygen to produce radicals, such as HO_2 , O_2^- , apart from other aqueous free radicals. The increase in the sensitivity of cells to ionizing radiation in the presence of oxygen, compared to that in its absence, is called the oxygen effect. The ratio of the dose required to achieve a given cell survival in the absence of oxygen to the dose required for the same effect under fully oxygenated conditions is called the oxygen enhancement ratio (OER), the value of which varies between 2.5 - 3 for X- and gamma- radiation. The effect of oxygen is said to be dose modifying and is independent of the radiation dose. Oxidative damage to the cellular genetic material, i.e., DNA, plays a major role in mutagenesis and carcinogenesis. Highly reactive oxygen radicals produced by ionizing radiation cause lesions in DNA which lead to cell killing and mutations. Enzymes such as superoxide dismutase, glutathione peroxidase and catalase protect mammalian cells from oxidative radiation damage7). It was recently reported that a cell line derived from a mutant strain of mouse having low cellular levels of temperature sensitive catalase activity is more sensitive to radiation and hydrogen peroxide.