Hypoxic cell radiosensitizers and local control by X-ray of a transplanted tumour in mice

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Abstract
Tumour experiments including local control after X-irradiation have been performed, using a new technique that eliminates the need for anaesthetics in restraining the animals. This system has been used to investigate the degree of sensitization that can be achieved with ICRF 159 and 4 strongly electron-affinic radiosensitizers, nifurpipone dihydrochloride, metronidazole, Ro-11-3696 and Ro-07-0582. No significant enhancement of the radiation effect was observed with ICRF 159. Significant sensitization was achieved by all 4 nitro-heterocyclic compoinds, Ro-07-0582 being the most effective, metronidazole and Ro-11-3696 the next, and nifurpipone dihydrochloride the least effective. For Ro-07-0582 and metronidazole, several concentrations were investigated, and the interval between injection with Ro-07-0582 and irradiation was varied: an interval of 30 min gave more sensitization than an interval of 90 min. The results from the local control experiments using Ro-07-0582 have been compared with those obtained from regrowth delay experiments. The radiosensitization obtained by the Ro-07-0582 increased with the X-ray dose above 25 gray. Both metronidazole and Ro-07-0582 gave significant enhancement effect at serum concentrations which can be achieved in man.