Modification of Tumour Response by Calcium Antagonists in the SCVII/St Tumour Implanted at Two Different Sites

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Abstract
Dose responses for the effects of four calcium antagonists on SCCVII/St back and leg tumour sensitivity to 20 Gy X-rays, and on tumour perfusion indicated by relative uptake of 86rubidium, were determined. The effects of these agents on 86rubidium uptake in some normal tissues were also investigated. Flunarizine sensitized tumours to X-rays over the dose range 0·005–500 mg/kg given i.p., but only small increases in tumour perfusion were seen at doses of 0·05–5 mg/kg. Verapamil increased tumour radioresistance at doses of 20 mg/kg and above, and reduced tumour perfusion at 50 mg/kg. Below 10 mg/kg, verapamil sensitized the tumours to X-rays, but produced little or no increase in tumour perfusion. Nifedipine at 10 mg/kg and above produced very radioresistant tumours, with correspondingly large reductions in tumour perfusion. At doses below 0·5 mg/kg sensitization was seen, but no increased tumour perfusion. Diltiazem at 50 mg/kg also increased tumour radioresistance with a reduction in tumour perfusion, and at lower doses sensitized tumours to X-rays, with small increases in tumour perfusion. The effects of these agents on normal tissues were varied and difficult to interpret. The similarity between the tumour radiation responses to the four calcium antagonists suggests that they may be acting upon the tumour vasculature in a manner independent of the systemic circulation.