Combinations of single doses and fractionated treatments of cis-dichlorodiammineplatinum (II) and irradiation: Effect on mouse lip mucosa

Tolerance of the lip mucosa of NMRI mice to single and fractionated irradiation combined with cis-diamminedichloroplatinum (II) (cis-DDP) was investigated. For the various combination schedules total drug doses varying from 6 mg kg^-1 to 13 mg kg^-1 were injected i.p. It was found that cis-DDP did not alter the radiation sensitivity of this tissue at any of the time intervals tested (ranging from 24 h before to 72 h after single dose irradiations). When 5 daily drug injections were given concomitantly with 5 daily radiation treatments, a slight reduction of the lip mucosal reactions occurred, possibly due to partial synchronisation during treatment. No effect was seen when a single injection of cis-DDP preceded two irradiations given with increasing intervals up to 4 h. Both these combined fractionated treatment data suggest no inhibitory effect on repair of sublethal radiation damage. When repeated daily injection of cis-DDP were given in between 2 radiation doses separated by 10 days, no interference with repopulation could be detected. The present study also demonstrated an increase in systemic drug toxicity when cis-DDP was combined with irradiation, compared with that seen with either agent alone