Chromosomal aberrations in peripheral blood lymphocytes from native Andean women and children from Northwestern Argentina exposed to arsenic in drinking water

Fernando N. Dulout , Claudia A. Grillo , Analía I. Seoane , Carlos R. Maderna , Robert Nilsson , Marie Vahter , Firouz Darroudi , Adayapalam T. Natarajan
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引用次数: 116

Abstract

For conducting an adequate human cancer risk assessment of inorganic arsenic (As) in the low-dose region, it is important to establish its mode of action. In this context, the nature of genotoxic effects induced by this agent is of considerable interest. However, the results from such investigations in human have been conflicting. In an attempt to resolve this issue, the clastogenic and aneugenic potential of As was investigated in women and children from native population exposed to high levels (around 0.2 mg/l) of natural As via drinking water in San Antonio de los Corbes in the Andean region of Salta, Northwestern Argentina. The water did not contain elevated levels of heavy metals, such as lead or cadmium, nor was the investigated population exposed to significant industrial pollution or to pesticides. An ethnically similar control group from Rosario de Lerma, Salta, where only extremely low concentration of arsenic in drinking water could be detected, was used as a control. To evaluate the genotoxic effects in peripheral blood lymphocytes, micronuclei (MN) in binucleated cells, sister-chromatid exchanges (SCEs) and the fluorescence in situ hybridization technique (FISH) in combination with chromosome specific DNA libraries were employed. The data obtained clearly indicate a highly significant increase in the frequency of MN and of trisomy in lymphocytes from exposed children and women in comparison with controls, but no notable effects were found on the frequencies of SCEs, specific translocations, or on cell cycle progression. As supported by FISH analysis, at least a proportion of MN appears to originate from whole chromosome loss. An additional finding was the unusually low background levels of MN in unexposed individuals from this ethnic group as compared to other populations, e.g., Caucasians.

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阿根廷西北部当地安第斯妇女和儿童接触饮用水中砷后外周血淋巴细胞的染色体畸变
为了在低剂量区域对无机砷(As)进行充分的人类癌症风险评估,确定其作用方式是很重要的。在这种情况下,这种药物引起的遗传毒性作用的性质引起了相当大的兴趣。然而,这类研究在人体中的结果却相互矛盾。为了解决这一问题,在阿根廷西北部萨尔塔安第斯地区的圣安东尼奥德洛斯科尔贝斯,研究了砷的致裂和致非优生潜力,这些妇女和儿童来自通过饮用水接触高水平(约0.2 mg/l)天然砷的土著人口。水中的重金属含量没有升高,比如铅或镉,被调查的人群也没有暴露在严重的工业污染或杀虫剂中。来自萨尔塔州罗萨里奥德勒马的一个种族相似的对照组被用作对照,那里的饮用水中只能检测到极低浓度的砷。为了评估其对外周血淋巴细胞的遗传毒性作用,采用了双核细胞微核(MN)、姐妹染色单体交换(SCEs)和荧光原位杂交技术(FISH)结合染色体特异性DNA文库的方法。获得的数据清楚地表明,与对照组相比,暴露的儿童和妇女淋巴细胞中MN和三体的频率显著增加,但对sce的频率、特异性易位或细胞周期进展没有明显影响。正如FISH分析所支持的那样,至少有一部分MN似乎源于整个染色体的丢失。另一个发现是,与其他人群(如高加索人)相比,该种族未暴露个体的锰背景水平异常低。
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