Lee I, Kim J H, Levitt S H, Song C W
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis 55455.
Int J Radiat Oncol Biol Phys. 1992;22(3):425-9. doi: 10.1016/0360-3016(92)90846-a.
Pentoxifylline (PENTO), a derivative of methylxanthine, has been reported to improve fluidity of red blood cells (RBC), and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO increases 2,3-DPG levels in RBC, thereby increasing the O2 release from RBC. Nicotinamide (NA) has been known to increase tumor blood flow, reducing the hypoxic cell fractions in the tumors. The purpose of this study was to examine the effects of PENTO alone or in combination with NA (PENTO + NA) on the oxygenation and radio-response of FSaII murine fibrosarcomas of mice. We observed a significantly enhanced, radiation-induced growth delay of the FSaII tumors by the treatment of either single or multiple injections of PENTO. The combination of PENTO and NA further delayed the growth of tumors. The TCD50 of control tumors was about 56.6 Gy, whereas that of PENTO + NA treated tumors was about 31.9 Gy. Thus, TCD50 was modified by a factor of 1.8. PENTO + NA exerted no effect on the acute skin damage of C3H mice after local irradiation and the gastrointestinal death after whole body irradiation. However, PENTO + NA slightly increased the bone marrow death as demonstrated by the decrease in LD50(30) from 5.5 Gy to 5.2 Gy. The average pO2 in the saline-treated control group of FSaII tumors was 8 mmHg and it significantly increased to 19 mmHg in the PENTO + NA treated group (p less than 0.001). We concluded that the PENTO + NA treatment increased the radio-response of tumors by improving tumor oxygenation.
己酮可可碱（PENTO）是甲基黄嘌呤的衍生物，据报道它能改善红细胞（RBC）的流动性，从而改善红细胞通过狭窄毛细血管的通量。此外，PENTO可提高红细胞内2,3-二磷酸甘油酸（2,3-DPG）水平，从而增加红细胞的氧释放。烟酰胺（NA）已知可增加肿瘤血流，减少肿瘤中的缺氧细胞比例。本研究的目的是探讨单独使用PENTO或与NA联合使用（PENTO + NA）对小鼠FSaII鼠纤维肉瘤的氧合和放射反应的影响。我们观察到，单次或多次注射PENTO治疗可显著增强FSaII肿瘤辐射诱导的生长延迟。PENTO与NA联合使用进一步延缓了肿瘤生长。对照肿瘤的TCD50约为56.6 Gy，而PENTO + NA治疗的肿瘤的TCD50约为31.9 Gy。因此，TCD50改变了1.8倍。PENTO + NA对局部照射后C3H小鼠的急性皮肤损伤和全身照射后的胃肠道死亡无影响。然而，PENTO + NA使骨髓死亡率略有增加，LD50(30)从5.5 Gy降至5.2 Gy即可证明。FSaII肿瘤生理盐水处理对照组的平均pO2为8 mmHg，而PENTO + NA治疗组显著增至19 mmHg（p < 0.001）。我们得出结论，PENTO + NA治疗通过改善肿瘤氧合增加了肿瘤的放射反应。
