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与核医学试剂盒相关的氯化亚锡诱导的细胞毒性和遗传毒性作用。

Cytotoxic and genotoxic effects induced by stannous chloride associated to nuclear medicine kits.

作者信息

Guedes Anderson P, Cardoso Valbert N, De Mattos Jose C P, Dantas Flavio J S, Matos Vanessa C, Silva Josiane C F, Bezerra Roberto J A C, Caldeira-de-Araujo Adriano

机构信息

Departamento de Biofísica e Biometria, Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro 20551-030, Brazil.

出版信息

Nucl Med Biol. 2006 Oct;33(7):915-21. doi: 10.1016/j.nucmedbio.2006.07.008.

Abstract

At present, more than 75% of routine nuclear medicine diagnostic procedures use technetium-99m (99mTc). The binding between 99mTc and the drug to obtain the radiopharmaceutical needs a reducing agent, with stannous chloride (SnCl2) being one of the most used. There are controversies about the cytotoxic, genotoxic and mutagenic effects of SnCl2 in the literature. Thus, the approaches below were used to better understand the biological effects of this salt and its association in nuclear medicine kits [methylenediphosphonate (MDP) bone scintigraphy and diethylenetriaminepentaacetic acid (DTPA) kidney and brain scintigraphy]: (i) bacterial inactivation experiments; (ii) agarose gel electrophoresis of supercoiled and linear plasmid DNA and (iii) bacterial transformation assay. The Escherichia coli strains used here were AB1157 (wild type) and BW9091 (xthA mutant). Data obtained showed that both MDP and SnCl2 presented a high toxicity, but this was not observed when they were assayed together in the kit, thereby displaying a mutual protect effect. DTPA salt showed a moderate toxicity, and once more, the DTPA kit provided protection, compared to the SnCl2 effect alone. The results suggest a possible complex formation, either MDP-SnCl2 or DTPA-SnCl2, originating an atoxic compound. On the other hand, SnCl2-induced cell inactivation and the decrease in bacterial transformation generated by DTPA found in XthA mutant strain suggest that the lack of this enzyme could be responsible for the effects observed, being necessary to induce DNA damage repair.

摘要

目前,超过75%的常规核医学诊断程序使用锝-99m(99mTc)。99mTc与药物结合以获得放射性药物需要一种还原剂,氯化亚锡(SnCl2)是最常用的还原剂之一。关于SnCl2的细胞毒性、遗传毒性和诱变效应,文献中存在争议。因此,采用以下方法来更好地了解这种盐及其在核医学试剂盒[亚甲基二膦酸盐(MDP)骨闪烁显像和二乙烯三胺五乙酸(DTPA)肾和脑闪烁显像]中的关联的生物学效应:(i)细菌灭活实验;(ii)超螺旋和线性质粒DNA的琼脂糖凝胶电泳;以及(iii)细菌转化试验。这里使用的大肠杆菌菌株是AB1157(野生型)和BW9091(xthA突变体)。获得的数据表明,MDP和SnCl2都具有高毒性,但当它们在试剂盒中一起检测时未观察到这种情况,从而显示出相互保护作用。DTPA盐显示出中等毒性,并且与单独的SnCl2效应相比,DTPA试剂盒再次提供了保护。结果表明可能形成了MDP-SnCl2或DTPA-SnCl2复合物,产生了一种无毒化合物。另一方面,SnCl2诱导的细胞灭活以及在XthA突变体菌株中发现的DTPA导致的细菌转化减少表明,这种酶的缺乏可能是观察到的效应的原因,诱导DNA损伤修复是必要的。

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