Chemical form of selenium, critical metabolites, and cancer prevention.
Chemical form of selenium, critical metabolites, and cancer prevention.
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发表时间：
1991-01
期刊：
影响因子：
11.2
通讯作者：
Clement Ip;Cassandra Hayes;R. M. Budnick;H. Ganther
中科院分区：
文献类型：
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作者：
Clement Ip;Cassandra Hayes;R. M. Budnick;H. Ganther
甲基化硒化物是膳食水平上的主要代谢物，用于利用硒获得抗癌作用。本研究报告了两种新型硒化合物（Se-甲基硒代半胱氨酸和二甲基硒氧化物）在大鼠二甲基苯并（a）蒽诱导的乳腺肿瘤模型中的化学预防活性。出于比较目的，其他治疗组补充亚硒酸盐或硒代胱氨酸。每种硒化合物都经过不同水平的测试，并在二甲基苯并(a)蒽给药前1周开始给予动物，并持续直至处死。致癌实验的结果表明，四种化合物的相对功效是Se-甲基硒代半胱氨酸大于亚硒酸盐，大于硒代半胱氨酸，大于二甲基硒氧化物。将这些硒化合物的化学形式和代谢与其抗癌活性联系起来，得出的结论是： (a) 能够产生稳定的甲基化代谢物流（特别是单甲基化物质）的硒化合物可能具有良好的化学预防潜力； (b) 硒代氨基酸的抗癌活性较低，例如从硒代半胱氨酸转化而来的硒代半胱氨酸，其通过随机、非化学计量掺入蛋白质而具有逃逸机制； (c) 硒的形式，例如氧化二甲基硒，它会快速、定量地代谢为二甲基硒化物和三甲基硒并排出体外，可能不是好的选择。我们还进行了一项单独的生物利用度研究，使用硒甲基硒代半胱氨酸、二甲基硒化物和三甲基硒作为起始化合物来输送具有一个、两个或三个甲基的硒，并测量了这些化合物恢复缺硒动物中谷胱甘肽过氧化物酶活性的能力。所有三种化合物都能够完全补充这种酶，尽管效率范围很广（Se-甲基硒代半胱氨酸大于二甲基硒氧化物大于三甲基硒），这表明完全去甲基化为无机硒是硒代谢的正常过程。然而，在化学预防条件下发生这种情况的程度可能会反对硒蛋白参与这些硒化合物的抗癌作用。
Methylated selenides are prominent metabolites at the dietary levels used for obtaining anticarcinogenic effects with selenium. The present study reports the chemopreventive activities of 2 novel selenium compounds, Se-methylselenocysteine and dimethyl selenoxide, in the rat dimethylbenz(a)anthracene-induced mammary tumor model. Other treatment groups were supplemented with either selenite or selenocystine for comparative purposes. Each selenium compound was tested at different levels and was given to the animal starting 1 week before dimethylbenz(a)anthracene administration and continued until sacrifice. Results of the carcinogenesis experiments showed that the relative efficacy with the four compounds was Se-methylselenocysteine greater than selenite greater than selenocystine greater than dimethyl selenoxide. In correlating the chemical form and metabolism of these selenium compounds with their anticarcinogenic activity, it is concluded that: (a) selenium compounds that are able to generate a steady stream of methylated metabolites, particularly the monomethylated species, are likely to have good chemopreventive potential; (b) anticarcinogenic activity is lower for selenoamino acids, such as selenocysteine following conversion from selenocystine, which have an escape mechanism via random, nonstoichiometric incorporation into proteins; and (c) forms of selenium, as exemplified by dimethyl selenoxide, which are metabolized rapidly and quantitatively to dimethyl selenide and trimethylselenonium and excreted, are likely to be poor choices. We also undertook a separate bioavailability study using Se-methylselenocysteine, dimethyl selenoxide, and trimethylselenonium as the starting compounds for delivering selenium with one, two, or three methyl groups, and measured the ability of these compounds to restore glutathione peroxidase activity in selenium-depleted animals. All three compounds were able to fully replete this enzyme, although with a wide range of efficiency (Se-methylselenocysteine greater than dimethyl selenoxide greater than trimethylselenonium), suggesting that complete demethylation to inorganic selenium is a normal process of selenium metabolism. However, the degree to which this occurs under chemoprevention conditions would argue against the involvement of selenoproteins in the anticarcinogenic action of these selenium compounds.