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9β-氯-16,16-二甲基前列腺素E2(诺氯前列素)对人正常成纤维细胞和结肠腺癌细胞辐射反应的差异作用。

Differential effect of 9 beta-chloro-16, 16-dimethyl prostaglandin E2 (nocloprost) on the radiation response of human normal fibroblasts and colon adenocarcinoma cells.

作者信息

Zaffaroni N, Villa R, Orlandi L, De Pascale A, Del Mastro S, Silvestrini R

机构信息

Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.

出版信息

Radiat Res. 1993 Jul;135(1):88-92.

PMID:8327666
Abstract

The possible influence of 9 beta-chloro-16,16-dimethyl prostaglandin E2 (nocloprost) on the effect of 137Cs gamma irradiation was investigated comparatively in human normal fibroblasts and colon adenocarcinoma cells. By itself, the compound did not influence the proliferation of cells of either cell type or the clonogenic capacity of carcinoma cells. Moreover, nocloprost did not induce any DNA strand breakage, as evaluated by neutral elution, in cells of either cell type. A 2-h incubation with nocloprost before irradiation induced an enhancement of fibroblast survival after an exposure of 10 Gy. This protective effect was not observed in adenocarcinoma cells under the same treatment conditions. The amount of double-strand breaks induced by 50 Gy was reduced in normal cells but not in tumor cells exposed to the prostaglandin analog before irradiation. Moreover, incubation with nocloprost for 2 h after irradiation remarkably enhanced the rate of rejoining of DNA breaks in fibroblasts but not in adenocarcinoma cells. Overall, these findings indicate a specific radioprotective effect of nocloprost in normal cells and no influence of the compound on the cytotoxic effect of ionizing radiation on colon adenocarcinoma cells.

摘要

在人正常成纤维细胞和结肠腺癌细胞中,比较研究了9β-氯-16,16-二甲基前列腺素E2(诺克洛前列素)对137Csγ射线照射效果的可能影响。该化合物本身对两种细胞类型的细胞增殖或癌细胞的克隆形成能力均无影响。此外,通过中性洗脱评估,诺克洛前列素在两种细胞类型的细胞中均未诱导任何DNA链断裂。照射前用诺克洛前列素孵育2小时,可使10 Gy照射后的成纤维细胞存活率提高。在相同处理条件下,腺癌细胞未观察到这种保护作用。照射前暴露于前列腺素类似物的正常细胞中,50 Gy诱导的双链断裂数量减少,但肿瘤细胞中未减少。此外,照射后用诺克洛前列素孵育2小时,可显著提高成纤维细胞中DNA断裂的重新连接率,但腺癌细胞中未提高。总体而言,这些发现表明诺克洛前列素对正常细胞具有特异性辐射保护作用,且该化合物对电离辐射对结肠腺癌细胞的细胞毒性作用无影响。

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