PURPOSE: In a previous study, the response of the R1H rhabdomyosarcoma of the rat to conventional irradiation (1.83-2.75 Gy fractions once-daily) and hyperfractionated radiotherapy (0.92-1.38 Gy fractions with different time intervals between the two daily fractions) was investigated [Kleineidam, M., Pieconka, A., Beck-Bornholdt, H.-P. Radiotherapy of the rhabdomyosarcoma R1H of the rat: influence of the time interval between two daily fractions during hyperfractionated radiotherapy. Radiother. Oncol. 30: 128-132, 1994]. Compared to once-daily irradiation, interfraction intervals of 2 h led to reduced tumour response, due to recovery from sublethal damage, and intervals of 5-6 h resulted in increased tumour response, possibly due to cell cycle effects. The purpose of the present study was to complement these tumour data by measuring clonogenic cell survival of R1H cells in vitro after split-dose irradiation. METHODS AND MATERIALS: Experiments were performed with 2 x 2.5 Gy and 2 x 3.5 Gy either at 21 degrees C (preventing cell cycle progression) or at 37 degrees C (allowing for cell cycle effects). RESULTS: For 3.5 Gy fractions, a cell survival curve equivalent to the in vivo results was obtained with the lowest surviving fraction observed at time intervals of 6-7 h, but only when cells were incubated at 37 degrees C during the interval. This phenomenon was absent in the 21 degrees C experiments. CONCLUSIONS: Our data provide further evidence to support the hypothesis that cell cycle effects are responsible for such observations. We conclude that the length of the interfraction interval has a considerable potential effect on tumour response to altered fractionation regimens.
