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Radiation protection by alpha-methyl-homocysteine thiolactone in vitro.

机译:α-甲基-高半胱氨酸硫代内酯在体外的辐射防护。

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摘要

The radiation protective effect of thiol compounds is unequivocal and their use is only limited by their toxic effects. We used the principle of alpha alkylation, which renders amino acids unmetabolizable, to reduce the toxicity of homocysteine. This product, alpha-methyl-homocysteine thio-lactone, was tested for toxicity and radiation protective effect along with known protectors L-cysteine, cysteamine and WR 1065 in cell culture using V79-4 Chinese hamster lung cells. The three-day growth curve assays, useful to measure overall effects on cell growth, revealed lowest toxicity for alpha-methyl-homocysteine thiolactone (GL-2). Clonogenic survival tests, used to evaluate the retention of reproductive integrity, were carried out and revealed that GL-2 had no adverse effects in this test system. Radiation protection tests showed that GL-2 exhibited protective activity against radiation induced lethality above that seen with cysteine and cysteamine, but below WR 1065. However, GL-2 showed little or no negative effects toward the cell itself, in direct contrast to WR 1065. Our findings show a potentially important tool and principle to reduce toxicity of radiation protectors with analogous structures.
机译:硫醇化合物的辐射防护作用是明确的,其使用仅受其毒性作用的限制。我们使用了α烷基化原理,使氨基酸不可代谢,从而降低了高半胱氨酸的毒性。在使用V79-4中国仓鼠肺细胞培养的细胞培养物中,测试了该产品α-甲基-高半胱氨酸硫代内酯的毒性和辐射防护效果,以及已知的保护剂L-半胱氨酸,半胱胺和WR 1065。为期三天的生长曲线测定法可用于测量对细胞生长的总体影响,显示出对α-甲基-半胱氨酸硫代内酯(GL-2)的最低毒性。进行了克隆生存性测试,用于评估生殖完整性的保持率,并发现GL-2在该测试系统中没有不良影响。辐射防护测试表明,GL-2在高于半胱氨酸和半胱胺的条件下,但在WR 1065以下,对辐射致死具有保护作用。但是,GL-2对细胞本身几乎没有或没有负面影响,与WR 1065直接相反我们的发现表明,减少具有类似结构的辐射防护装置的毒性可能具有潜在的重要工具和原理。

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