RADIO AND CHEMO SENSITIZATION DEPENDENCE ON OXYGEN

低氧细胞限制了固体细胞成功控制的可能性 放射肿瘤学家已经认识到X射线治疗肿瘤已经超过 25年 认识到缺氧可能是一个限制因素， 化疗是最近才开始的 试图克服的阻力 低氧细胞对放射治疗的反应导致了“低氧细胞”的发展 敏化剂”，即模拟氧气并与辐射相互作用的药物， 特别是增加缺氧细胞的敏感性。 这些致敏剂 优先杀死具有时间依赖性细胞毒性的缺氧细胞。 这 细胞毒性是“预孵育效应”的基础， 缺氧细胞暴露于致敏药物增强了它们的杀伤作用， 放射和癌症化学治疗剂。 意图营利使 这些试剂的预孵育作用在临床上是有利的， 较低剂量的敏化剂可全身使用以增强 放疗和化疗药物。 氧在这种增强作用中的作用 这一点很重要，因为它可能有助于解释 动物和细胞培养系统，并且可以模拟中间水平的 氧气有望在实体瘤中发现。 K因子的确定 放射和化学敏化将具有实用价值， 评估这些致敏化合物的最有效使用。 计划用仓鼠和人类来源的哺乳动物细胞进行实验， 调查和比较在预孵育暴露中氧的水平 导致放射和化学敏感。 用几种2 和4-硝基咪唑随后将暴露于增加剂量的 X射线或博来霉素、顺式-DDP、L-PAM、PALA和BCNU。 浆细胞 膜也将作为预孵育效应的目标进行分析， 测定预处理细胞中Na、Mg和Ca-ATP酶的水平。 使用 预孵育效应，以增强对缺氧细胞的杀伤 对药物和放射治疗有抵抗力， 在实体瘤治疗中的贡献。

The possibility that hypoxic cells limit the successful control of solid tumors by x-rays has been recognized by radiation oncologists for more than 25 years. The realization that hypoxia may be a limiting factor in chemotherapy is much more recent. Attempts to overcome the resistance of hypoxic cells to radiotherapy have led to the development of "hypoxic cell sensitizers", drugs that mimic oxygen and interact with radiation to specifically increase the sensitivity of hypoxic cells. These sensitizers preferentially kill hypoxic cells with a time-dependent cytotoxicity. This cytotoxicity is the basis of the "preincubation effect" where prolonged exposure of hypoxic cells to sensitizing drugs enhances their killing by radiation and cancer chemotherapeutic agents. Exploitation of the preincubation effect of these agents can be clinically advantageous where lower doses of sensitizer can be used systemically to enhance the action of radiation and chemotherapy drugs. The role of oxygen in this potentiation is important because it may help to explain differences found between animal and cell culture systems, and may mimic the intermediate levels of oxygen expected to be found in solid tumors. Determination of the K factor for radio- and chemo- sensitization would be of practical value in evaluating the most effective use of these sensitizing compounds. Experiments with mammalian cells of hamster and human origin are planned to investigate and compare what levels of oxygen in a preincubation exposure result in radio- and chemo- sensitization. Cells pretreated with several 2 and 4-nitroimidazoles will be subsequently exposed to increasing doses of x-rays or Bleomycin, Cis-DDP, L-PAM, PALA, and BCNU. The plasma cell membrane will also be analyzed as a target of the preincubation effect by assaying for levels of Na, Kg Mg, and Ca-ATPase in pretreated cells. Use of the preincubation effect, to enhance the killing of hypoxic cells resistant to drug and radiation therapy, can make a significant contribution in the treatment of solid tumors.