COMPARISON OF SELENIUM AND SULFUR ANALOGS IN CANCER PREVENTION
COMPARISON OF SELENIUM AND SULFUR ANALOGS IN CANCER PREVENTION
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DOI：
10.1093/carcin/13.7.1167
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发表时间：
1992-07-01
期刊：
影响因子：
4.7
通讯作者：
GANTHER, HE
中科院分区：
文献类型：
--
作者：
IP, C;GANTHER, HE
几种有机硒化合物已被证明具有很强的抗癌活性。鉴于硒和硫的生物化学有一定的相似性，我们利用7，12-二甲基苯并[a]菲(DMBA)诱发的大鼠乳腺肿瘤模型，评价了三种类似物的化学预防效果。被测试的化合物是硒半胱胺/半胱胺、硒-甲基硒半胱氨酸/S-甲基半胱氨酸、硒甜菜碱/磺基甜菜碱。在第一项研究中，将每种制剂添加到基础AIN-76A饮食中，并在DMBA治疗之前和之后继续给药，直到结束。三种硒化合物均有活性；硒-甲基半胱氨酸和硒甜菜碱的抑制率约为25×10~(-6)m o l/kg，而硒的抑制率约为40×10~(-6)m ol/kg。在硫系列中，只有半胱胺和S-甲基半胱氨酸产生抗癌活性，与相应的硒类似物相比，可比反应所需的水平高500-750倍。磺胺甜菜碱即使在接近最大耐受量的情况下也是无效的。在第二项研究中，选择了Se-甲基硒半胱氨酸和S-甲基半胱氨酸在乳腺癌发生的起始和启动后阶段进行了进一步的检测。甲基硒半胱氨酸在DMBA给药前或给药后均有效。相反，S-甲基半胱氨酸只有在DMBA治疗后才有效。因此，与硫结构类似物相比，硒化合物在防癌方面更具活性，在防止细胞转化以及延缓或抑制致癌物暴露后的恶性肿瘤表达方面可能具有多模式机制。
Several organoselenium compounds have been shown to have powerful anticarcinogenic activity. In view of certain similarities between selenium and sulfur biochemistry, we have evaluated the chemopreventive efficacy of three pairs of analogs using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats. The compounds tested were selenocystamine/cysteamine, Se-methylselenocysteine/S-methylcysteine, selenobetaine/sulfobetaine. In the first study, each agent was added to the basal AIN-76A diet and was given before and continued after DMBA treatment until the end. All three selenium compounds were active; a 50% inhibition was achieved at approximately 25 X 10(-6) mol/kg with Se-methylselenocysteine and selenobetaine and at approximately 40 X 10(-6) mol/kg with selenoxystamine. In the sulfur series, only cysteamine and S-methylcysteine produced anticancer activity, and the levels required for comparable responses were 500- to 750-fold higher compared to the corresponding selenium analogs. Sulfobetaine was inactive even when present at near maximally tolerated levels. In the second study, Se-methylselenocysteine and S-methylcysteine were chosen for further examination during the initiation and post-initiation phases of mammary carcinogenesis. Se-Methylselenocysteine was effective when it was given either before or after DMBA administration. In contrast, S-methylcysteine was effective only after DMBA treatment. Thus, compared to the sulfur structural analogs, selenium compounds are much more active in cancer protection and may have a multi-modal mechanism in preventing cellular transformation as well as in delaying or inhibiting the expression of malignancy after carcinogen exposure.