Hydralazine-induced tumor hypoxia: a potential target for cancer chemotherapy.
Currently available cancer chemotherapeutic agents have been designed to exploit subtle differences in proliferation and biochemistry that are known to exist between host and malignant cells. However, chemotherapeutic agents may also be used to exploit physiological differences between cancer and normal tissue. The present study was conducted to determine whether the reduction in blood flow to the tumor (and thus oxygen delivery) induced by the vasodilator hydralazine would increase the cytotoxicity of drugs known to be more toxic in regions of reduced oxygenation. Results obtained with three murine tumor models clearly demonstrate that hydralazine potentiates the tumor cytotoxicity of such agents to a greater extent than it does their systemic toxicity. This study indicates a potential strategy for increasing the efficacy of certain cancer chemotherapeutic agents in solid tumors.
Chaplin
D J
DJ
Medical Biophysics Unit, British Columbia Cancer Research Centre, Vancouver, Canada.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001388:Aziridines / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D006830:Hydralazine / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008920:Misonidazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D008937:Mitomycins / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy; D012039:Regional Blood Flow / Q000187:drug effects
D000970:Antineoplastic Agents; D001388:Aziridines; D008937:Mitomycins; D006830:Hydralazine; C100099:tretazicar; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole