低水平甲基汞诱导大鼠DNA损伤：硒的保护作用。
Low levels of methylmercury induce DNA damage in rats: protective effects of selenium.
作者信息
Grotto Denise, Barcelos Gustavo R M, Valentini Juliana, Antunes Lusânia M G, Angeli José Pedro F, Garcia Solange C, Barbosa Fernando
机构信息
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, Campus Universitário da USP, 14040-903, Ribeirão Preto, São Paulo, Brazil.
出版信息
Arch Toxicol. 2009 Mar;83(3):249-54. doi: 10.1007/s00204-008-0353-3. Epub 2008 Aug 27.
In this study we examined the possible antigenotoxic effect of selenium (Se) in rats chronically exposed to low levels of methylmercury (MeHg) and the association between glutathione peroxidase (GSH-Px) activity and DNA lesions (via comet assay) in the same exposed animals. Rats were divided into six groups as follows: (Group I) received water; (Group II) received MeHg (100 mug/day); (Group III) received Se (2 mg/L drinking water); (Group IV) received Se (6 mg/L drinking water); (Group V) received MeHg (100 mug/day) and Se (2 mg/L drinking water); (Group VI) received MeHg (100 mug/day) and Se (6 mg/L drinking water). Total treatment time was 100 days. GSH-Px activity was determined spectrophotometrically and DNA damage was determined by comet assay. Mean GSH-Px activity in groups I, II, III, IV, V and VI were, respectively: 40.19 +/- 17.21; 23.63 +/- 6.04; 42.64 +/- 5.70; 38.50 +/- 7.15; 34.54 +/- 6.18 and 41.39 +/- 11.67 nmolNADPH/min/gHb. DNA damage was represented by a mean score from 0 to 300; the results for groups I, II, III, IV, V and VI were, respectively: 6.87 +/- 3.27; 124.12 +/- 13.74; 10.62 +/- 3.81; 13.25 +/- 1.76; 86.87 +/- 11.95 and 76.25 +/- 7.48. There was a significant inhibition of GSH-Px activity in group II compared with group I (P < 0.05). Groups V and VI did not show a difference in enzyme activity compared with groups III and IV, showing the possible protective action of Se. Comet assay presented a significant difference in DNA migration between group II and group I (P < 0.0001). Groups V and VI showed a significant reduction in MeHg-induced genotoxicity (P < 0.001) when compared with group II. A negative correlation (r = -0.559, P < 0.05) was found between GSH-Px activity and DNA lesion, showing that the greater the DNA damage, the lower the GSH-Px activity. Our findings demonstrated the oxidative and genotoxic properties of MeHg, even at low doses. Moreover, Se co-administration reestablished GSH-Px activity and reduced DNA damage.
在本研究中，我们检测了长期暴露于低水平甲基汞（MeHg）的大鼠体内硒（Se）可能的抗遗传毒性作用，以及同一暴露组动物中谷胱甘肽过氧化物酶（GSH-Px）活性与DNA损伤（通过彗星试验）之间的关联。大鼠被分为六组，如下：（第一组）饮用纯水；（第二组）接受MeHg（100μg/天）；（第三组）接受Se（2mg/L饮用水）；（第四组）接受Se（6mg/L饮用水）；（第五组）接受MeHg（100μg/天）和Se（2mg/L饮用水）；（第六组）接受MeHg（100μg/天）和Se（6mg/L饮用水）。总治疗时间为100天。采用分光光度法测定GSH-Px活性，通过彗星试验测定DNA损伤。第一、二、三、四、五和六组的平均GSH-Px活性分别为：40.19±17.21；23.63±6.04；42.64±5.70；38.50±7.15；34.54±6.18和41.39±11.67nmolNADPH/分钟/gHb。DNA损伤用0至300的平均评分表示；第一、二、三、四、五和六组的结果分别为：6.87±3.27；124.12±13.74；10.62±3.81；13.25±1.76；86.87±11.95和76.25±7.48。与第一组相比，第二组的GSH-Px活性受到显著抑制（P<0.05）。与第三组和第四组相比，第五组和第六组的酶活性没有差异，表明Se可能具有保护作用。彗星试验显示第二组和第一组之间的DNA迁移存在显著差异（P<0.0001）。与第二组相比，第五组和第六组显示出MeHg诱导的遗传毒性显著降低（P<0.001）。发现GSH-Px活性与DNA损伤之间存在负相关（r=-0.559，P<0.05），表明DNA损伤越大，GSH-Px活性越低。我们的研究结果证明了即使在低剂量下MeHg的氧化和遗传毒性特性。此外，联合使用Se可恢复GSH-Px活性并减少DNA损伤。
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