Effect of methylated forms of selenium on cell viability and the induction of DNA strand breakage.
Effect of methylated forms of selenium on cell viability and the induction of DNA strand breakage.
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DOI：
10.1016/0006-2952(92)90622-p
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发表时间：
1992-03
影响因子：
5.8
通讯作者：
Adrian C. Wilson;Henry J. Thompson;P. Schedin;Neil W. Gibson;H. Ganther
中科院分区：
文献类型：
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作者：
Adrian C. Wilson;Henry J. Thompson;P. Schedin;Neil W. Gibson;H. Ganther
硒甜菜碱(SB)和硒甜菜碱甲酯(SBME)是甲基化硒的衍生物，它们经过代谢分别释放甲基硒和二甲基硒作为主要代谢物。由于硒的甲基化被认为是解毒的，Sb或SBME的毒理活性可能不同于无机形式的硒，如亚硒酸盐，后者经历还原并可诱导细胞损伤。本研究比较了Sb、SBME和亚硒酸钠对小鼠白血病细胞系L1210的存活率和长期生长能力的影响。用20μM亚硒酸盐处理细胞后，细胞倍增率和细胞长期生长能力(以克隆形成能力衡量)均降低。亚硒酸盐的这些作用伴随着DNA完整性的降低，通过单链断裂的碱性洗脱分析进行评估。在不影响染料排斥或诱导μ单链断裂的情况下，暴露于500dna、M、SB或sBME 24小时会降低细胞的集落形成能力。细胞暴露于500μM、Sb或SBME后，细胞内的硒水平与20μM亚硒酸盐暴露后的水平相似。这些观察表明，在不影响DNA完整性的情况下，通过暴露于甲基化的含硒化合物，可以维持细胞内高水平的硒。这些发现还表明，接触亚硒酸盐导致的DNA片段化发生在其还原代谢过程中，而不是由于硒的甲基化代谢产物的积累。SB或SBME在没有DNA碎裂的情况下降低了L1210细胞在琼脂中形成集落的能力，也没有对处理细胞排除活性染料的能力产生任何影响，这一事实表明，这两种甲基化化合物都通过一种不同于细胞损伤和坏死死亡的机制改变了细胞的长期增殖潜力(S)。目前正在努力确定这些影响的来源。
Selenobetaine (SB) and selenobetaine methyl ester (SBME) are methylated selenonium derivatives that undergo metabolism to release methyl selenide and dimethylselenide, respectively, as primary metabolites. Since methylation of selenium is considered to be detoxifying, the toxicologic activity of SB or SBME may differ from that of inorganic forms of selenium, such as selenite, that undergo reduction and can induce cell damage. In this study, the effects of SB, SBME and selenite on the viability and long-term growth potential of a mouse leukemia cell line (L1210) were compared. Treatment with 20 μM selenite reduced the rate of cell doubling and the long-term growth potential of cells as measured by colony-forming ability. These effects of selenite were accompanied by a reduction in DNA integrity, assessed by alkaline elution analysis for single-strand breaks. Exposure to 500 μM SB or SBME for 24 hr reduced the colony-forming ability of cells in the absence of any effect on dye exclusion or induction of single-strand breaks in DNA. Exposure of cells to 500 μM SB or SBME resulted in levels of intracellular selenium similar to those after exposure to 20 μM selenite. These observations indicate that it is possible to maintain high intracellular levels of selenium, by exposure to methylated selenocompounds, without affecting DNA integrity. These findings also suggest that DNA fragmentation resulting from exposure to selenite occurs during its reductive metabolism and not from the accumulation of a methylated metabolite of selenium. The fact that SB or SBME reduced the ability of L1210 cells to form colonies in agar in the absence of either DNA fragmentation or any effect on the ability of treated cells to exclude a vital dye suggests that both methylated compounds alter the longterm proliferative potential of cells via a mechanism(s) distinct from that associated with cell injury and death by necrosis. Efforts are underway to determine the origin of these effects.