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长期饮用含砷酸盐的水对C57Bl/6J小鼠的遗传毒性作用以及低硒饮食对这些作用的调节。

Genotoxic effects in C57Bl/6J mice chronically exposed to arsenate in drinking water and modulation of the effects by low-selenium diet.

作者信息

Palus Jadwiga, Lewińska Dobrosława, Dziubałtowska Elzbieta, Wasowicz Wojciech, Gromadzińska Jolanta, Rydzyński Konrad, Stańczyk Małgorzata, Arkusz Joanna, Trzcinka-Ochocka Małgorzata, Stepnik Maciej

机构信息

Nofer Institute of Occupational Medicine, Łódź, Poland.

出版信息

J Toxicol Environ Health A. 2006 Oct;69(20):1843-60. doi: 10.1080/15287390600631490.

DOI:10.1080/15287390600631490
PMID:16952904
Abstract

In C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or 500 microg As/L, genotoxic effects in bone-marrow cells using micronucleus test and in peripheral blood leukocytes using the comet assay were determined after 3, 6 or 12 mo. To assess the modulating role of selenium in development of the effects, the animals were fed a specially prepared low-selenium diet and were supplemented with sodium selenite (200 microg Se/L) in drinking water (supplemented groups) or were without Se supplementation (nonsupplemented groups). Measurements of glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma were performed after 3, 6, and 12 mo and showed a marked decrease in values in animals in non-Se supplemented compared to Se-supplemented groups. After 3 mo of arsenic exposure in the Se-supplemented animals the level of DNA fragmentation (without Endo III and Fpg enzymes) did not differ from the control; however, increased oxidative damage of purine and pyrimidine bases was observed. In groups not supplemented with Se, an increase of DNA fragmentation was observed; however, the levels of oxidative DNA damage in these groups did not differ from the control. None of the positive effects observed in the comet assay after 3 mo was related to arsenate concentration. The levels of DNA damage after 6 and 12 mo of exposure to arsenic as well as the frequency of micronuclei after 3, 6, and 12 mo did not differ significantly between exposed and control animals, irrespective of Se supplementation status.

摘要

在以50、200或500微克砷/升的浓度长期饮用含砷酸盐的水的C57Bl/6J小鼠中,在3、6或12个月后,使用微核试验测定骨髓细胞中的遗传毒性效应,并使用彗星试验测定外周血白细胞中的遗传毒性效应。为了评估硒在这些效应发展中的调节作用,给动物喂食特制的低硒饮食,并在饮用水中补充亚硒酸钠(200微克硒/升)(补充组)或不补充硒(未补充组)。在3、6和12个月后测量红细胞和血浆中的谷胱甘肽过氧化物酶活性以及血浆中的硒浓度,结果显示,与补充硒的组相比,未补充硒的动物的这些值显著降低。在补充硒的动物中,砷暴露3个月后,DNA片段化水平(无内切酶III和Fpg酶)与对照组无差异;然而,观察到嘌呤和嘧啶碱基的氧化损伤增加。在未补充硒的组中,观察到DNA片段化增加;然而,这些组中的氧化性DNA损伤水平与对照组无差异。在彗星试验中3个月后观察到的任何阳性效应均与砷酸盐浓度无关。无论硒补充状态如何,暴露组和对照组动物在砷暴露6个月和12个月后的DNA损伤水平以及在3个月、6个月和12个月后的微核频率均无显著差异。

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