Mitchell J B, Cook J A, Krishna M C, DeGraff W, Gamson J, Fisher J, Christodoulou D, Wink D A
Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Br J Cancer Suppl. 1996 Jul;27:S181-4.
Previous studies have shown that nitric oxide (NO) sensitises hypoxic cells to ionising radiation. In the present study, four different nitric oxide (NO) donor agents were evaluated for both NO release and hypoxic radiosensitisation. The S-nitrosothiol NO donor agents, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to release sustained NO concentrations (microM) and significantly radiosensitise hypoxic cells. The extent of hypoxic radiosensitisation by both of these agents at 1.0 mM concentration was similar to that obtained with molecular oxygen. In contrast, neither 3-morpholinosydnonimine (SIN-1) nor sodium nitroprusside (SNP) released detectable NO concentrations and neither agent enhanced the hypoxic radiation response to the extent of that observed for GSNO or SNAP. NO-mediated hypoxic cell radiosensitisation by NO donor drugs may offer a new approach for clinical consideration, particularly if such agents can be selectively delivered to hypoxic cells.
先前的研究表明，一氧化氮（NO）可使缺氧细胞对电离辐射敏感。在本研究中，对四种不同的一氧化氮（NO）供体药物进行了NO释放和缺氧放射增敏作用的评估。结果显示，亚硝基硫醇类NO供体药物，即亚硝基谷胱甘肽（GSNO）和亚硝基-N-乙酰青霉胺（SNAP），能够持续释放NO浓度（微摩尔），并显著使缺氧细胞对辐射敏感。这两种药物在1.0 mM浓度下的缺氧放射增敏程度与分子氧所产生的增敏程度相似。相比之下，3-吗啉代-1,2,3-噻二唑（SIN-1）和硝普钠（SNP）均未释放出可检测到的NO浓度，且两种药物均未像GSNO或SNAP那样增强缺氧辐射反应。NO供体药物介导的NO对缺氧细胞的放射增敏作用可能为临床治疗提供一种新方法，特别是如果此类药物能够选择性地作用于缺氧细胞。
