Horsman M R, Chaplin D J, Brown J M
Department of Radiation Oncology, Stanford University Medical Center, California 94305.
Radiat Res. 1989 Apr;118(1):139-50.
Nicotinamide has been shown to sensitize tumors to radiation in preference to normal tissues. We have extended our studies to examine the mechanism responsible for this radiosensitization, using the EMT6 tumor model. Our results confirm that nicotinamide (1000 mg/kg) significantly enhances the radiation damage in this tumor when given as a single intraperitoneal injection 90 min before irradiation. The data also show that nicotinamide does not directly sensitize hypoxic cells to radiation either in vitro or in vivo. Excising tumors immediately after irradiation and exposing them to nicotinamide (7 mM) for 24 h similarly failed to increase the radiation damage, implying that nicotinamide does not inhibit the repair of radiation-induced potentially lethal damage. Nicotinamide did, however, produce a decrease in the binding of [14C]-misonidazole in tumors, consistent with a reduction in the degree of tumor hypoxia. There was also an increase in mean tumor cell fluorescence of Hoechst 33342 in nicotinamide-treated mice compared to that of controls, suggesting that the increase in tumor oxygenation was probably a consequence of an increase in tumor blood perfusion.
已证明烟酰胺可使肿瘤对辐射敏感，而对正常组织的影响较小。我们利用EMT6肿瘤模型扩展了研究，以探究这种放射增敏作用的机制。我们的结果证实，在照射前90分钟腹腔注射一次烟酰胺（1000毫克/千克），可显著增强该肿瘤的辐射损伤。数据还表明，烟酰胺在体外或体内均不会直接使缺氧细胞对辐射敏感。照射后立即切除肿瘤，并将其暴露于烟酰胺（7毫摩尔）中24小时，同样未能增加辐射损伤，这意味着烟酰胺不会抑制辐射诱导的潜在致死性损伤的修复。然而，烟酰胺确实使肿瘤中[14C]-米索硝唑的结合减少，这与肿瘤缺氧程度的降低一致。与对照组相比，烟酰胺处理的小鼠中Hoechst 33342的平均肿瘤细胞荧光也有所增加，这表明肿瘤氧合增加可能是肿瘤血流灌注增加的结果。
