The inhibition of radiation-induced mutagenesis by the combined effects of selenium and the aminothiol WR-1065
The inhibition of radiation-induced mutagenesis by the combined effects of selenium and the aminothiol WR-1065
复制标题
DOI：
10.1016/0027-5107(96)00016-4
复制
发表时间：
1996-09-23
影响因子：
2.3
通讯作者：
Grdina, DJ
中科院分区：
文献类型：
--
作者：
Diamond, AM;Dale, P;Grdina, DJ
为了评估潜在化学保护化合物硒和(S)-2-（3-氨基丙基氨基）乙基硫代酸（WR-1065）的抗诱变作用，在照射前将这两种化合物单独或联合暴露于CHO AA8细胞。通过在这些细胞的hprt位点检测到的突变定量来评估暴露于8 Gy后的突变频率。30 nM亚硒酸钠和4 mM WR-1065对辐照诱变均有保护作用。此外，这些药物的组合提供的抗突变诱导的保护似乎是附加的。相比之下，亚硒酸钠单独或与WR-1065联合使用时均不能提供抗辐射毒性的保护。为了评估在这些细胞中观察到的抗诱变作用的可能机制，在暴露于化学预防化合物后评估了谷胱甘肽过氧化物酶（GPx）的活性。在培养基中添加亚硒酸钠可使GPx活性增加5倍，而WR-1065的存在对GPx活性没有影响。来自这些细胞的RNA的Northern分析表明，硒补充导致细胞质GPx (GSHPx-1) mRNA的边际增加，这不足以解释在细胞提取物中观察到的GPx活性的刺激。这些结果表明，硒和WR-1065通过独立的机制发挥保护作用，GPx刺激可能是硒抗诱变作用的机制之一。
In order to evaluate the anti-mutagenic effects of the potential chemoprotective compounds selenium and (S)-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-1065), CHO AA8 cells were exposed to both compounds either individually or in combination prior to irradiation. Mutation frequency following exposure to 8 Gy was evaluated by quantitation of the mutations detected at the hprt locus of these cells. Protection against radiation-induced mutation was observed for both 30 nM sodium selenite or 4 mM WR-1065. In addition, the protection against mutation induction provided by the combination of these agents appeared additive. In contrast, sodium selenite did not provide protection against radiation toxicity when provided either alone or in conjunction with WR-1065. In order to evaluate the possible mechanisms of the anti-mutagenic effects observed in these cells, glutathione peroxidase (GPx) activity was evaluated following exposure to the chemopreventative compounds. The addition of sodium selenite to the culture media resulted in a 5-fold increase in GPx activity, which was unaltered by the presence of the WR-1065. Northern analysis of RNA derived from these cells indicated that selenium supplementation resulted in a marginal increase in the mRNA for the cytosolic GPx (GSHPx-1) which was insufficient to account for the stimulation of GPx activity observed in cellular extracts. These results suggest that selenium and WR-1065 offer protection via independent mechanisms and that GPx stimulation remains a possible mechanism of the anti-mutagenic effect of selenium.