Severin E, Hagenhoff B
Institut für Strahlenbiologie, Universität Münster.
Strahlenther Onkol. 1988 Mar;164(3):165-72.
In this article, some arguments are put forward which support the conception of a combined radio-chemotherapy acting by a reversible inhibition of tumor cells with cytostatic drugs in a not cytocidal dose and the following selective killing by irradiation of the cells blocked in a radiosensitive phase. The two cytostatic drugs 5-fluorouracil (FU) and vinblastine (VLB), as inhibitors of DNA synthesis and mitosis, respectively, are tested in vitro both separately and combined in two tumor cell lines of the mouse, i.e. the Ehrlich ascites tumor and the sarcoma S 180. A cell-proliferative and, as far as possible, not cytocidal dose is used because of the inevitable side effects exerted by these drugs on normal tissues. A reversible synchronization of the ascites tumor is achieved even in the young mouse by FU in a dose of 15 ng to 500 ng (applied seven times every two hours), if the synchronization is controlled by applying the antimetabolite together with uracil in an equimolar concentration and then stimulating the growth of the cells inhibited during DNA synthesis by the administration of thymidine. The statistical analysis of dose-effect curves after X-ray irradiation shows an increased radiosensitivity of the synchronized cell population, provided that the optimum moment had been chosen for the irradiation.
本文提出了一些观点,支持联合放化疗的概念,即先用细胞抑制药物以非杀细胞剂量可逆性抑制肿瘤细胞,然后通过照射使处于放射敏感期的细胞被阻断,进而实现选择性杀伤。分别以两种细胞抑制药物5-氟尿嘧啶(FU)和长春碱(VLB)作为DNA合成抑制剂和有丝分裂抑制剂,在小鼠的两种肿瘤细胞系,即艾氏腹水瘤和肉瘤S 180中进行体外单独及联合试验。由于这些药物对正常组织不可避免地会产生副作用,所以使用细胞增殖性且尽可能非杀细胞的剂量。如果通过以等摩尔浓度将抗代谢物与尿嘧啶一起应用,然后通过给予胸苷刺激在DNA合成过程中受到抑制的细胞生长来控制同步化,那么即使在幼鼠中,15纳克至500纳克剂量的FU(每两小时给药7次)也能使腹水瘤实现可逆性同步化。对X射线照射后的剂量效应曲线进行统计分析表明,只要选择了最佳照射时刻,同步化细胞群体的放射敏感性就会增加。