Tumor blood flow changes induced by chemical modifiers of radiation response.
This study was designed to investigate blood flow changes induced by chemical agents that are commonly used in combination with radiation therapy. The hypoxic cell cytotoxin RSU 1069 at a dose of 100 mg/kg was shown to reduce blood flow by 80% in both SCCVII and C3H mammary tumors. Blood flow reductions of 30-40% were also observed in both tumors following administration of the radiation sensitiser pimonidazole (Ro-03-8799) at a dose of 500 mg/kg. Moreover studies in the C3H mammary tumor indicated that this effect was tumor size-dependent, being more profound and of longer duration in 500 mg than in 100 mg tumors. Blood flow decreases were also observed in the SCCVII tumor after administration of adriamycin at a dose of 15 mg/kg. Blood flow decreased by over 80% immediately after drug administration but recovered to remain 20% below control values 1 hr after drug administration. In contrast to the other agents studied, cis platinum at a dose of 2 mg/kg produced a small 20-30% increase in blood flow which persisted over the 1 hr observation period. The potential implications of these findings are discussed.
Chaplin
D J
DJ
Medical Biophysics Unit, B C Cancer Research Centre, Vancouver, Canada.
Horsman
M R
MR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000031:analogs & derivatives / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000503:physiopathology; D009593:Nitroimidazoles / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole; D004317:Doxorubicin; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; D002945:Cisplatin