Kim S H, Khil M S, Ryu S, Kim J H
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI.
Int J Radiat Oncol Biol Phys. 1993 Jan;25(1):61-5. doi: 10.1016/0360-3016(93)90145-l.
Pentoxifylline, a methylxanthine, has been shown to improve tumor tissue oxygenation in hypoxic murine tumors and prevent the late radiation injury of normal tissues in mice. The present cell culture studies were carried out to determine whether pentoxifylline would enhance the cellular radiation response of several human carcinoma cells in culture under various culture conditions.
Experiments were carried out with three human carcinoma cells grown in Eagle's MEM supplemented with 10% FCS. Cell survival was assayed by the colony forming ability of single plated cells to obtain dose-survival curves.
Cells irradiated and exposed to pentoxifylline for 24 hr showed a significant enhancement of radiation-induced cytotoxicity. Pre-irradiation treatment with the drug did not change cellular response to radiation. The magnitude of radiation enhancement was dependent on the concentration of drug and exposure time up to the time corresponding to one cell cycle time. Among the three human carcinoma cells used (HeLa S-3 cervix carcinoma, MCF-7 breast carcinoma, and HT-29 colon carcinoma), HeLa S-3 cells were most susceptible to the combined treatment with the enhancement ratio of 1.4 at 1 mM. Among the derivatives of methylxanthines, caffeine and pentoxifylline were equally effective on a molar basis. The combined effect of pentoxifylline and purine nucleosides, including guanosine and deoxyguanosine, further enhanced the sensitizing effect of pentoxifylline.
The present data along with other radiobiological effects of the drug suggest that pentoxifylline should be considered as a radiation enhancer for clinical radiotherapy.
己酮可可碱，一种甲基黄嘌呤，已被证明可改善缺氧小鼠肿瘤中的肿瘤组织氧合，并预防小鼠正常组织的晚期放射损伤。本细胞培养研究旨在确定己酮可可碱在各种培养条件下是否会增强培养的几种人癌细胞的细胞辐射反应。
实验使用在补充有10%胎牛血清的伊格尔氏MEM培养基中生长的三种人癌细胞进行。通过单个接种细胞的集落形成能力测定细胞存活率，以获得剂量-存活曲线。
照射后暴露于己酮可可碱24小时的细胞显示出辐射诱导的细胞毒性显著增强。药物预照射处理未改变细胞对辐射的反应。辐射增强的程度取决于药物浓度和暴露时间，直至对应于一个细胞周期时间。在所使用的三种人癌细胞（HeLa S-3宫颈癌、MCF-7乳腺癌和HT-29结肠癌）中，HeLa S-3细胞对联合治疗最敏感，在1 mM时增强比为1.4。在甲基黄嘌呤的衍生物中，咖啡因和己酮可可碱在摩尔基础上同样有效。己酮可可碱与嘌呤核苷（包括鸟苷和脱氧鸟苷）的联合作用进一步增强了己酮可可碱的增敏作用。
目前的数据以及该药物的其他放射生物学效应表明，己酮可可碱应被视为临床放射治疗的辐射增强剂。
