DNA stability and serum selenium levels in a high-risk group for prostate cancer.

DNA stability and serum selenium levels in a high-risk group for prostate cancer.
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DOI:
10.1158/1055-9965.391.13.3
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发表时间:
2004-03
期刊:
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子:
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通讯作者:
N. Karunasinghe;J. Ryan;J. Tuckey;J. Masters;M. Jamieson;L. Clarke;J. Marshall;L. Ferguson
N. Karunasinghe;J. Ryan;J. Tuckey;J. Masters;M. Jamieson;L. Clarke;J. Marshall;L. Ferguson
中科院分区:
其他
文献类型:
--
作者:
N. Karunasinghe;J. Ryan;J. Tuckey;J. Masters;M. Jamieson;L. Clarke;J. Marshall;L. Ferguson

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新西兰饮食中的基本微量营养素硒含量很低。硒是参与维持基因组稳定性的许多蛋白质的组成部分,并且推荐的每日摄入量(RDA)被设定为谷胱甘肽过氧化物酶(GPx)的饱和水平,谷胱甘肽过氧化物酶是监测氧化应激的关键酶。这是假设,但没有证明,这一水平将是足够的其他关键硒酶。“阴性活检试验”确定了一组新西兰前列腺癌高危人群,将监测其血清硒水平,并在较长时间内补充含硒或不含硒的酵母片剂。在这项试验中接触患者提供了一个机会,可以问一个更一般的问题,即该人群中的硒水平是否足以维持基因组的稳定性。单细胞凝胶电泳(彗星)测定用于研究从这些志愿者收集的血液白细胞中的DNA损伤。随机分组前的平均血清硒水平为97.8 +/- 16.6 ng/ml,低于国际标准。对于低于该平均值的一半人群,较低的血清硒水平与总体累积DNA损伤呈统计学显著负相关(P = 0.02)。虽然不能排除其他解释,但数据表明,该人群中有一半人的硒摄入量对于DNA损伤的充分修复来说是微不足道的,增加了对癌症和其他退行性疾病的易感性。它还提出了一个问题,即谷胱甘肽过氧化物酶饱和水平是否是特定人群最佳硒水平的适当指标。
The essential micronutrient, selenium, is at low levels in the New Zealand diet. Selenium is a component of a number of proteins involved in the maintenance of genomic stability, and recommended daily allowances (RDA) are set on saturation levels for glutathione peroxidase (GPx), a key enzyme in surveillance against oxidative stress. It has been assumed but not proven that this level will be adequate for other key selenoenzymes. The "Negative Biopsy Trial" identifies a group of New Zealand individuals at high risk of prostate cancer, whose serum selenium levels will be monitored and who will be supplemented with a yeast-based tablet, with or without selenium, over an extended time. Access to patients on this trial provides the opportunity to ask the more generic question as to whether selenium levels in this population are adequate to maintain genomic stability. The single cell gel electrophoresis (comet) assay was used to study DNA damage in blood leukocytes harvested from these volunteers. Average serum selenium levels before randomization was 97.8 +/- 16.6 ng/ml, low by international standards. For the half of the population below this mean value, lower serum selenium levels showed a statistically significant inverse relationship (P = 0.02) with overall accumulated DNA damage. Although other interpretations cannot be excluded, the data suggest that the selenium intake in half of this population is marginal for adequate repair of DNA damage, increasing susceptibility to cancer and other degenerative diseases. It also raises the question as to whether glutathione peroxidase saturation levels are appropriate indicators of the optimal selenium levels for a given population.