Effects of a perfluorochemical emulsion on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation.
The effects of the combination of a perfluorochemical emulsion (Fluosol DA, 20%) and carbogen (95% O2, 5% CO2) on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation were examined. Tumors were irradiated locally in unrestrained, unanesthetized rats at a dose rate of 0.98 Gy/h, using a specially designed 241Am irradiator system. Cell survival was measured using a colony formation assay. The tumor cell survival curves were fitted to linear relationships of the form ln S = - alpha D, where alpha for air-breathing rats was 0.104 +/- 0.005 Gy-1, as compared to 0.137 +/- 0.009 Gy-1 for rats treated with Fluosol plus carbogen. The increase in the slope of the survival curve produced by the treatment with Fluosol and carbogen was highly significant with a P value of 0.0015. The radiosensitization factor for the combination of Fluosol/carbogen plus continuous low-dose-rate irradiation was 1.32 +/- 0.11. Slightly less radiosensitization was observed with continuous low-dose-rate irradiation than in previous experiments using acute high-dose-rate irradiation. The diminished sensitization with Fluosol/carbogen during continuous low-dose-rate irradiation probably reflects the intrinsically lower oxygen enhancement ratio (OER) of low-dose/low-dose-rate irradiation, reoxygenation of the tumors during the prolonged treatment times used for continuous low-dose-rate irradiation, and the decrease in the levels of circulating perfluorochemicals during the 30-h irradiations. More importantly, the significant level of radiosensitization observed in the experiments with continuous low-dose-rate irradiation suggests that hypoxic cells persist in BA1112 tumors during continuous low-dose-rate irradiations and that the response of these tumors to continuous low-dose-rate irradiation can be improved by adjunctive treatments which oxygenate these radioresistant hypoxic tumor cells.
Morton
J D
JD
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510-8040.
Porter
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Yabuki
H
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Nath
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Rockwell
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D000576:Americium; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004338:Drug Combinations; D005466:Fluorocarbons / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives; D008297:Male; D010100:Oxygen / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011879:Radiotherapy Dosage; D051381:Rats; D012208:Rhabdomyosarcoma / Q000503:physiopathology / Q000532:radiotherapy*; D013997:Time Factors
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; C011700:carbogen; D010100:Oxygen; D000576:Americium