REPAIR, REDISTRIBUTION AND REPOPULATION IN V79 SPHEROIDS DURING MULTIFRACTION IRRADIATION

Development of predictive assays for measuring tumour radiosensitivity has generated much recent interest, particularly with the recognition that tumour cell survival at doses of about 2 Gy may correlate well w ith tumour curability. Clinical data, however, suggest that overall tr eatment time may be of considerable significance in radioresponsive tu mours, especially for rapidly growing tumours capable of accelerated r epopulation. Because neither factor can be repeatedly assessed in huma n tumours, we used cells growing as multicell spheroids to determine w hether the initial radiation response would be predictive for multifra ction exposures, or whether other factors including repopulation rate should be considered. Potential problems of hypoxia and reoxygenation were avoided by using small spheroids which had not yet developed radi obiologically hypoxic regions. Repair and redistribution dominated the responses in the first two or three exposures, with repopulation play ing a minor role. As the fractionation schedule was extended, however, repopulation between fractions largely determined the number of viabl e cells per spheroid. We conclude that the radiation response of cells from untreated spheroids provides a general indication of net sensiti vity, but that repair and redistribution produces considerable variati on in radiosensitivity throughout a fractionation protocol. Ultimately , repopulation effects may dominate the multifraction response.