Tumor radiation responses and tumor oxygenation in aging mice.
EMT6 mouse mammary tumors transplanted into aging mice are less sensitive to radiation than are tumors growing in young adult animals. We hypothesized previously that this reflected a greater proportion of radiation resistant, hypoxic cells in the tumors of aging animals. The experiments reported here compare the radiation dose-response curves defining the survivals of tumor cells in aging mice and in young adult mice. Cell survival curves were assessed in normal air-breathing mice and in mice which had been asphyxiated with N2 to produce uniform hypoxia throughout the tumors. Analyses of these survival curves revealed that 41% of the viable malignant cells were severely hypoxic in tumors in aging mice, while only 19% of the tumor cells in young adult animals were radiobiologically hypoxic. This did not appear to reflect anemia in the old animals, as the hematocrits of young and aging tumor-bearing animals were similar. Treatment of aging animals with a perfluorochemical emulsion plus carbogen (95% O2/5% CO2) increased the radiation response of the tumors, apparently by improving tumor oxygenation and thereby decreasing the number of severely hypoxic, radiation resistant cells in the tumors.
Rockwell
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Yale University School of Medicine, Department of Therapeutic Radiology, New Haven, Connecticut 06510-8040.
D000367:Age Factors; D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology; D002460:Cell Line; D004338:Drug Combinations / Q000494:pharmacology; D005466:Fluorocarbons / Q000494:pharmacology; D006895:Hydroxyethyl Starch Derivatives; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010101:Oxygen Consumption; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination