Hypoxic cell radiosensitizers

Adams GE, Flockhart IR, Smithen CE, Stratford IJ, Wardman P, Watts ME (1976a) Electron-affinic sensitization. VII. A correlation between structures, one-electron reduction potentials, and efficiencies of nitroimidazoles as hypoxic cell radiosensitizers. Radiat Res 67 9-20... 

Adams GE, Clarke ED, Flockhart IR, Jacobs RS, Sehmi DS, Stratford IJ, Wardman P, Watts ME, Parrick J, Wallace RG, Smithen CE (1979) Structure-activity relationships in the development of hypoxic cell radiosensitizers. I. Sensitization efficiency. Int J Radiat Biol 35 133-150... 

Wardman P (1977) The use of nitroaromatic compounds as hypoxic cell radiosensitizers. Curr Top Radiat Res 011 347-398... 

Wardman P (1984) Radiation chemistry in the clinic Hypoxic cell radiosensitizers for radiotherapy. 

High-performance liquid chromatography (HPLC) has been used to analyze metronidazole [1435-1437], misonidazole [1309,1438], and other nitroimidazoles [1435, 1439] in body fluids or pharmaceutical dosage forms. HPLC analysis of effect of hypoxic-cell radiosensitizer misonidazole on the radiation-induced reduction of DNA bases (thymine, cytosine, and adenine) has been carried out [1440, 1441], HPLC was employed to characterize different nitroimidazoles [327, 366, 388,409, 450, 1442-1444], nitropyrazoles [246, 301], nitrothiazoles [366], l-aryl(hetaryl)-4-nitro-l,2,3-triazoles [601], nitrobenzimidazoles [707], nitrobenzofurazans [774, 1445-1449], nitrobenzotriazoles [1450],... 

Properties 2-Nitroimidazole hypoxic cell radiosensitizer mf C8H12N404. 

When it was recognized that the clastogenic effect of this phorbol diester involved the release of superoxide, clastogenicity was suppressed and cell survival increased by concomitant incubation with Cu-Zn SOD [497-499]. Pretreatment with Cu-Zn SOD also reduced X-ray and phorbol diester promoted transformations and increased survival of culture hamster embryo cells [493, 500]. In still another study it was found that Cu-Zn SOD reduced transformation of lOTl/2 cells produced by concomitant X-ray irradiation and exposure to misonidazole, a hypoxic cell radiosensitizer [501]. These observations were most pronounced when Cu-Zn SOD was present during fixation and expression periods [502], consistent with the observation that Cu-Zn SOD protects DNA [503] and proteins [474] against ionizing radiation. Effective radiation protection as a result of superoxide removal does offer anticlastogenic activity as well. 

Drugs to enhance radiation sensitivity are of clinical value only if there is selectivity towards the tumour compared to normal tissues unavoidably included in the radiation field in radiotherapy. The drugs discussed briefly below -hypoxic cell radiosensitizers - present such selectivity mainly because oxygen is such an efficient radio sensitizer that in well-oxygenated tissues its effect is virtually at a maximum, and added oxygen-mimetic drugs have very little additional effect. 

Quantitative structure-activity relationships (QSARs) for hypoxic cell radiosensitizers... 

Although activity in the search for inqiroved hypoxic cell radiosensitizers has decreased, the contribution of radiation chemistry in defining the range of reduction potentials which are needed for effective radiosensitizers was seminal. 

G.E. Adams, I. Ahmed, E.D. Clarke, P. O Neill, J. Parrick, I.J. Stratford, R.G. Wallace, P. Wardman and M.E. Watts, Structure-activity relationships in the development of hypoxic cell radiosensitizers, in. Effects of basic substituents in nitroimidazole side-chains, Int. J. Radiat. Biol., 38 (1980) 613. 

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