The effect of radiation on the growth of normal and malignant human oesophageal explant cultures pre-treated with bleomycin

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Abstract
Since all known chemotherapy and radiation treatments affect normal cells to a certain extent, the establishment of favourable differential sensitivities is fundamental to the success of treatment with a particular agent. This type of information can be gained by animal testing and using cultured cells, but ultimately use of the agent in the patient is the only way to determine the response. We have developed a model for testing the response of oesophageal explants from tumour and surrounding normal tissue in the same patient to chemotherapy and radiation, both singly and in combination. The test allows treatment combinations, time and order of administration of agents to the tissue to be accurately controlled. Cytotoxicity, determined by measuring the area of outgrowth from an explant 2 weeks after plating, is the most useful short-term end-point, although many others are possible. Results showing the differential cytotoxicity of bleomycin with and without radiation in squamous and adenocarcinoma of the oesophagus and surrounding normal tissue from the same patient indicate that tumour cells are relatively resistant to radiation alone, that low levels of bleomycin with or without radiation preferentially spare tumour cells and that high levels, in combination with any dose of radiation tested, but not without radiation, spare the normal cells and give a significantly high amount of relative tumour cell kill. Bleomycin must be added to the cells just before or just after irradiation to obtain the normal-tissue sparing effect. The technique may be a useful method for indicating the best approaches to the optimization of combined therapy regimes.