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利用彗星试验研究重铬酸钾对小鼠白细胞的体内遗传毒性作用。

In vivo genotoxic effect of potassium dichromate in mice leukocytes using comet assay.

作者信息

Dana Devi K, Rozati R, Saleha Banu B, Jamil K, Grover P

机构信息

Deccan College of Medical Sciences and Owaisi Hospital and Research Centre, Hyderabad, Andrhra Pradesh, India.

出版信息

Food Chem Toxicol. 2001 Aug;39(8):859-65. doi: 10.1016/s0278-6915(01)00019-9.

DOI:10.1016/s0278-6915(01)00019-9
PMID:11434993
Abstract

Hexavalent chromium is a well-known mutagen and carcinogen. In the present investigation, single-/double-stranded DNA breaks by potassium dichromate (K2Cr2O7) in mice, a sensitive model for genotoxic effects, have been studied in vivo using alkaline single-cell gel electrophoresis (SCGE)/comet assay. Mice were administered orally with a range of doses starting from 0.59 to 76.0 mg/kg body weight of K2Cr2O7 and samples of whole blood were collected at 24, 48, 72, 96 h, week 1 and week 2 post-treatment for alkaline SCGE assay to study DNA damage. The rationale for using leukocytes was to reflect biomarker analysis in humans. Significant increase in mean comet tail length (5.7-24.25 microM) indicating DNA damage was observed at all the doses with K2Cr2O7 when compared with controls (3.26 microM). Maximum increase in mean comet tail length was observed at 9.5 mg/kg body weight at 48 h post-treatment (24.25 microM). The mean comet tail length showed a clear dose-dependent increase from 0.59 to 9.5 mg/kg body weight and a dose-dependent decrease in higher doses (19.0-76.0 mg/kg body weight). A gradual decrease in the tail lengths from 72 h post-treatment was observed by the second week, and values had returned to control levels at all doses, indicating repair of the damaged DNA and/or loss of heavily damaged cells. The study also reveals that comet assay is a sensitive and rapid method for detecting DNA damage caused by heavy metals such as chromium (Cr).

摘要

六价铬是一种著名的诱变剂和致癌物。在本研究中,使用碱性单细胞凝胶电泳(SCGE)/彗星试验在体内研究了重铬酸钾(K2Cr2O7)对小鼠单链/双链DNA的断裂作用,小鼠是一种用于遗传毒性效应的敏感模型。给小鼠口服一系列剂量的K2Cr2O7,起始剂量为0.59至76.0毫克/千克体重,并在处理后的24、48、72、96小时、第1周和第2周采集全血样本进行碱性SCGE试验,以研究DNA损伤。使用白细胞的理由是反映人类的生物标志物分析。与对照组(3.26微米)相比,在所有K2Cr2O7剂量下均观察到平均彗星尾长显著增加(5.7 - 24.25微米),表明存在DNA损伤。在处理后48小时,体重为9.5毫克/千克时观察到平均彗星尾长增加最多(24.25微米)。平均彗星尾长在体重从0.59至9.5毫克/千克时呈明显的剂量依赖性增加,而在较高剂量(19.0 - 76.0毫克/千克体重)时呈剂量依赖性下降。从处理后72小时到第二周观察到尾长逐渐减少,并且所有剂量下的值均恢复到对照水平,表明受损DNA得到修复和/或严重受损细胞丢失。该研究还表明,彗星试验是检测铬(Cr)等重金属引起的DNA损伤的一种灵敏且快速的方法。

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