Koch Cameron J, Oprysko Patricia R, Shuman A Lee, Jenkins W Timothy, Brandt Gordon, Evans Sydney M
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072, USA.
Cancer Res. 2002 Jul 1;62(13):3626-9.
One method to make hypoxic, radioresistant cells more radiation sensitive has been to increase the oxygen carrying capacity of normal blood using liquid perfluorochemical emulsions combined with breathing high pO2 gases. We investigated the ability of dodecafluoropentane (DDFP) to sensitize the moderately radiation-resistant Morris 7777 hepatoma based on our previous inability to modify the radiation response of this tumor. DDFP is used in very small quantities compared with perfluorchemicals reported previously. Rats under isoflurane anesthesia were administered EF5 3 h before irradiation to monitor the pretreatment level of tissue hypoxia. At -40 min, DDFP was administered i.v. at 3.5 ml/kg over 30 min. At -10 min, the rats were either continued with air (for controls) or switched to carbogen. The tumors were then irradiated and processed for evaluation of radiation response. Tumor-cell survival for DDFP treatment with air-breathing animals was not significantly different from controls treated without DDFP. Carbogen alone provided minimal sensitization. DDFP plus carbogen caused dramatic radiosensitization, and the radiation response of cells from these tumors was the same as a completely aerobic radiation response. DDFP plus carbogen appears to completely reverse the hypoxic cell radioresistance in this tumor model.
使缺氧的、具有放射抗性的细胞对辐射更敏感的一种方法是，使用全氟化合物液体乳剂并结合呼吸高氧分压气体来提高正常血液的携氧能力。基于我们之前无法改变这种肿瘤的辐射反应，我们研究了十二氟戊烷（DDFP）使中度放射抗性的莫里斯7777肝癌细胞敏感化的能力。与之前报道的全氟化合物相比，DDFP的用量非常少。在异氟烷麻醉下的大鼠在照射前3小时给予EF5，以监测组织缺氧的预处理水平。在 -40分钟时，以3.5毫升/千克的剂量在30分钟内静脉注射DDFP。在 -10分钟时，大鼠要么继续呼吸空气（作为对照），要么切换到混合气。然后对肿瘤进行照射并处理以评估辐射反应。呼吸空气的动物接受DDFP治疗后的肿瘤细胞存活率与未接受DDFP治疗的对照没有显著差异。单独使用混合气产生的增敏作用最小。DDFP加混合气引起了显著的放射增敏作用，并且这些肿瘤细胞的辐射反应与完全有氧的辐射反应相同。在这个肿瘤模型中，DDFP加混合气似乎完全逆转了缺氧细胞的放射抗性。
