Cellular radiosensitization: principles and methods of study

The development and use of oxygen mimetic radiosensitizing drugs is arguably one of the major contributions of radiobiology and radiation chemistry to the treatment of the cancer patient by radiotherapy. This progress is based on fundamental physical-chemical and radiation-chemical observations, which allowed the testing of hypoxic cell radiosensitizing drugs in spores and vegetative bacteria and finally in in vitro mammalian cell systems. The demonstration of radiosensitization of hypoxic mammalian cells in vitro promptly stimulated the in vivo testing of suitable compounds which has resulted in the clinical evaluation of the best compounds developed to date viz. misonidazole and metronidazole. This chapter takes a cursory look at the in vitro mammalian cell methods used to evaluate the potential of any particular compound for use as a radiosensitizer. This includes an examination of the radiosensitizing effect on various in vitro cell systems together with the effects of different qualities of radiation. The methods used to equate the sensitizing efficiency of any compounds with the physical-chemical properties of that compound (i.e., the formulation of structure-activity relationships) are discussed. Finally the toxicity of potential radiosensitizers is reviewed, and this includes the discussion of the different hypoxic cell toxicity seen with the nitroaromatic radiosensitizers and speculation as to the possible role of nitroaromatic compounds in combination chemotherapy. (Auth.)