The effect of cisplatin on the repair of radiation damage in RIF1 mouse tumours in vivo.

ABSTRACT

The effect of the antitumour agent cisplatin on repair of X-ray-induced damage was studied in RIF1 mouse tumours treated in situ. The response of tumours, assessed by growth delay, to 4 fractions of X-rays given at 5-h intervals was compared with that after single doses. The displacement between the curves was taken as a measure of repair. A single dose of 6 mg.kg-1 cisplatin given 0.5 h before the first fraction resulted in no detectable inhibition of repair despite a significant growth delay caused by drug alone. A dose of 2 mg/kg cisplatin given 0.5 h before each of the X-ray fractions did, however, cause some repair inhibition; a result confirmed by tumour control experiments. The schedule dependence for repair inhibition was the same whether the irradiations were carried out on clamped (fully hypoxic) tumours or under ambient conditions. Significant enhancement of radiation damage was seen after correcting for the effects of drug alone, whether or not repair inhibition occurred. The effects of cisplatin on normal stroma within the tumour (vascular damage) was also investigated by monitoring the regrowth rates of recurrent tumours. In contrast to the effects on tumour cells, no enhancement of damage or inhibition of repair was seen for this assay in the combined treatment schedules.