Rockwell S
Yale University School of Medicine, Department of Therapeutic Radiology, New Haven, Connecticut 06510-8040.
Exp Gerontol. 1989;24(1):37-48. doi: 10.1016/0531-5565(89)90033-8.
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.
移植到老龄小鼠体内的EMT6小鼠乳腺肿瘤对辐射的敏感性低于在年轻成年动物体内生长的肿瘤。我们之前推测，这反映出老龄动物肿瘤中具有辐射抗性的低氧细胞比例更高。本文报道的实验比较了定义老龄小鼠和年轻成年小鼠肿瘤细胞存活率的辐射剂量反应曲线。在正常呼吸空气的小鼠以及用氮气窒息以在整个肿瘤中产生均匀低氧的小鼠中评估细胞存活曲线。对这些存活曲线的分析显示，老龄小鼠肿瘤中41%的存活恶性细胞处于严重低氧状态，而年轻成年动物肿瘤中只有19%的肿瘤细胞在放射生物学上处于低氧状态。这似乎并不反映老龄动物存在贫血，因为年轻和老龄荷瘤动物的血细胞比容相似。用全氟化合物乳剂加卡波金（95%氧气/5%二氧化碳）治疗老龄动物可提高肿瘤的辐射反应，这显然是通过改善肿瘤氧合，从而减少肿瘤中严重低氧、具有辐射抗性的细胞数量来实现的。
