Cinnarizine and flunarizine as radiation sensitisers in two murine tumours.
The effect of the calcium antagonists, cinnarizine and flunarizine on the radiation sensitivity of two murine tumours, RIF-1 and SCCVII/St was investigated. Initial experiments giving the compounds at 50 mg kg-1 i.p. indicated that cinnarizine had no effect on cell survival after 20 Gy of X-rays in the RIF-1 sarcoma and only a small effect in the SCCVII/St carcinoma. However, flunarizine produced a small radiosensitisation in the RIF-1 tumour and a substantial sensitisation in the SCCVII/St tumour. Subsequent experiments in the SCCVII/St tumour indicated that the optimal radiosensitising dose of flunarizine was approximately 5 mg kg-1, although some sensitisation was apparent throughout the range of 0.05-500 mg kg-1. Flunarizine produced a parallel shift in the X-ray dose response curve, equivalent to a 5-fold reduction in hypoxic fraction. In a normal tissue study, 5 mg kg-1 flunarizine did not enhance the reduction in white cell counts produced by X-ray doses of 2-8 Gy. These data suggest that flunarizine may have some potential use as a radiosensitiser.
Wood
P J
PJ
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Hirst
D G
DG
D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002936:Cinnarizine / Q000627:therapeutic use*; D005260:Female; D005444:Flunarizine / Q000627:therapeutic use*; D007958:Leukocyte Count; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D011879:Radiotherapy Dosage; D012513:Sarcoma, Experimental / Q000532:radiotherapy; D013997:Time Factors
D011838:Radiation-Sensitizing Agents; D002936:Cinnarizine; D005444:Flunarizine