Calcium antagonists as radiation modifiers: site specificity in relation to tumor response.
The calcium antagonists, verapamil, nifedipine, and flunarizine, were studied for their effects on blood flow and radiation response in SCCVII/St intradermal back tumors, over a dose range of 0.05-50 mg/kg. Verapamil, at low doses, increased tumor blood flow, as measured by relative fluorescence intensity of Ho33342 stain, and increased tumor radiosensitivity. However, at doses of 20 mg/kg and above, verapamil reduced Ho33342 fluorescence intensity, and increased tumor radioresistance. Nifedipine reduced tumor radiosensitivity and Ho33342 fluroscence intensity at doses above 1 mg/kg, but below this dose increased Ho33342 intensity was observed and a small radiosensitization was apparent. Flunarizine sensitized tumors to X rays at all doses tested, although increased Ho33342 intensity was seen only at 5 mg/kg. The relative affinities of these compounds for different sites within the host may explain the variations in blood flow and radiation sensitivity in this tumor system.
Wood
P J
PJ
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Hirst
D G
DG
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005444:Flunarizine / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000532:radiotherapy*; D009543:Nifedipine / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents; D014700:Verapamil / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D011838:Radiation-Sensitizing Agents; D014700:Verapamil; D009543:Nifedipine; D005444:Flunarizine