Hedley David W, Nicklee Trudey, Moreno-Merlo Fernando, Pintilie Melania, Fyles Anthony, Milosevic Michael, Hill Richard P
Department of Medical Oncology and Hematology, Toronto, ON, Canada.
Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):137-44. doi: 10.1016/j.ijrobp.2004.02.020.
The non-protein sulfydryls (NPSH) glutathione and cysteine are able to effect chemical repair of radiation-induced DNA damage, particularly under hypoxic conditions, and are implicated in radioresistance. The levels of NPSH in the nucleus are predicted to be more important than those in cytoplasm. We, therefore, investigated the relation between nuclear NPSH and the clinical outcome of radical radiotherapy (RT).
A fluorescence image analysis technique to measure nuclear NPSH was developed, based on the SH-reactive probe 1(4-chloromercuryphenyl-azo-2-naphthol) and the DNA dye 4,6-diamidino-2-phenylindole. This was used to measure nuclear and tissue NPSH levels in biopsies obtained from 58 patients with locally advanced uterine cervical carcinoma, treated with radical RT.
An approximately twofold range in the nuclear and tissue NPSH levels between individual tumors was found, although the intratumoral heterogeneity was much smaller. Nuclear and tissue NPSH values correlated closely in all cases. No statistically significant associations were noted between NPSH levels and tumor size, stage, or tumor hypoxia as determined at the time of biopsy using an Eppendorf po(2) probe. The response to RT and patient survival did not correlate with tumor NPSH.
These results did not support the existence of an independently regulated nuclear pool of NPSH and showed that tissue and nuclear NPSH are not predictive of the outcome of patients with locally advanced cervical carcinomas treated with RT.
非蛋白质巯基（NPSH）谷胱甘肽和半胱氨酸能够对辐射诱导的DNA损伤进行化学修复，尤其是在缺氧条件下，并且与放射抗性有关。据预测，细胞核中的NPSH水平比细胞质中的更重要。因此，我们研究了细胞核NPSH与根治性放疗（RT）临床结果之间的关系。
基于SH反应性探针1（4-氯汞苯基偶氮-2-萘酚）和DNA染料4,6-二脒基-2-苯基吲哚，开发了一种用于测量细胞核NPSH的荧光图像分析技术。该技术用于测量58例接受根治性RT治疗的局部晚期子宫颈癌患者活检组织中的细胞核和组织NPSH水平。
尽管肿瘤内异质性要小得多，但在各个肿瘤之间发现细胞核和组织NPSH水平存在约两倍的差异范围。在所有病例中，细胞核和组织NPSH值密切相关。使用Eppendorf po(2) 探针在活检时测定，NPSH水平与肿瘤大小、分期或肿瘤缺氧之间未发现统计学上的显著关联。对RT的反应和患者生存率与肿瘤NPSH无关。
这些结果不支持存在独立调节的细胞核NPSH池，并表明组织和细胞核NPSH不能预测接受RT治疗的局部晚期宫颈癌患者的预后。
