Correlation between radiosensitivity, percentage hypoxic cells and pO2 measurements in one rodent and two human tumor xenografts.
Computerized pO2 histography has been used to measure the intratumor pO2 in patients for the past few years, and there is now evidence that these tumors contain hypoxic cells. One of the major questions that remains to be answered is the relevance of such data to radiosensitivity. The present study looks for a correlation between intratumor pO2, the percentage of hypoxic cells in the tumor and the radiosensitization induced by carbogen and/or the oxygen carrier, perflubron emulsion. Two human tumor xenografts (HRT18, Na11+) and one rodent tumor (EMT6) were used. The radiosensitivity (clonogenic assay) and the oxygen tension (computerized pO2 histography) were measured. All experiments were performed under similar conditions. Carbogen increased tumor radiosensitivity; sensitization was greatest when 4 ml/kg perflubron emulsion was used in conjunction with carbogen. The pO2 distribution was shifted to higher pO2 values in the tumors whatever the treatment; the shift was greater for perflubron emulsion plus carbogen. The low pO2 values (< 0.4 kPa) were lost for the HRT18 cells. A correlation (EMT6, HRT18) or a link (Na11+) between the radiosensitization and the oxygen tension measurements was found for values below 1.07 or 1.33 kPa. A trend between the percentage of hypoxic cells and pO2 measurements was found taking into account pO2 measurements comprised between 0.27 and 0.67 kPa.
Laboratoire de Radiobiologie Cellulaire (Unité Inserm 247), Institut Gustave-Roussy, Villejuif, France.
C D
CD
Thomas
N
N
Chavaudra
L
L
Martin
M
M
Guichard
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D001237:Asphyxia; D002245:Carbon Dioxide / Q000494:pharmacology; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes; D004307:Dose-Response Relationship, Radiation; D004655:Emulsions; D005466:Fluorocarbons / Q000494:pharmacology; D005720:Gamma Rays; D006801:Humans; D006842:Hydrocarbons, Brominated; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010100:Oxygen / Q000032:analysis* / Q000494:pharmacology; D010313:Partial Pressure; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012004:Rectal Neoplasms / Q000473:pathology*; D012119:Respiration; D014183:Transplantation, Heterologous
D002588:Cesium Radioisotopes; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; C003072:perflubron; D010100:Oxygen