Radiosensitization of hypoxic tumor cells by dodecafluoropentane: a gas-phase perfluorochemical emulsion.

Radiosensitization of hypoxic tumor cells by dodecafluoropentane: a gas-phase perfluorochemical emulsion.
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DOI:
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发表时间:
2002-07
期刊:
影响因子:
11.2
通讯作者:
C. Koch;P. Oprysko;A. Shuman;W. T. Jenkins;G. Brandt;S. Evans
C. Koch;P. Oprysko;A. Shuman;W. T. Jenkins;G. Brandt;S. Evans
中科院分区:
医学1区
文献类型:
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作者:
C. Koch;P. Oprysko;A. Shuman;W. T. Jenkins;G. Brandt;S. Evans

文献摘要

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使缺氧、抗辐射的细胞对辐射更加敏感的一种方法是使用液体全氟化物乳剂结合呼吸高 pO2 气体来增加正常血液的携氧能力。基于我们之前无法改变这种肿瘤的放射反应,我们研究了十二氟戊烷 (DDFP) 使中等耐辐射的 Morris 7777 肝癌增敏的能力。与之前报道的全氟化学品相比,DDFP 的使用量非常少。异氟烷麻醉下的大鼠在照射前3 h给予EF5以监测治疗前组织缺氧水平。在-40分钟时,静脉注射DDFP。 3.5 毫升/公斤,持续 30 分钟。在-10分钟时,大鼠要么继续吸入空气(作为对照),要么改用卡波金。然后对肿瘤进行照射和处理以评估放射反应。呼吸空气的动物经 DDFP 处理后的肿瘤细胞存活率与未经 DDFP 处理的对照组没有显着差异。单独使用卡波金可产生最小的致敏作用。 DDFP加卡波金引起显着的放射增敏作用,这些肿瘤细胞的放射反应与完全有氧放射反应相同。 DDFP 加卡波金似乎完全逆转了该肿瘤模型中的缺氧细胞放射抗性。
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.