二甲基次胂酸促小鼠皮肤肿瘤发生与诱发氧化应激 |
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引用本文: | 安艳,李贞,王三祥,王正辉,商希梅,乔建维. 二甲基次胂酸促小鼠皮肤肿瘤发生与诱发氧化应激[J]. 卫生研究, 2009, 38(3) |
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作者姓名: | 安艳 李贞 王三祥 王正辉 商希梅 乔建维 |
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作者单位: | 1. 苏州大学医学部放射医学与公共卫生学院,苏州,215123 2. 山东省医学科学院 3. 山西省地方病防治研究所 |
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基金项目: | 国家自然科学基金,教育部留学回国人员科研启动基金,人事部留学人员科技活动项目择优资助课题,日本文部科学省资助项目 |
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摘 要: | 目的研究二甲基次胂酸对小鼠皮肤促肿瘤发生与诱发氧化应激之间的关系。方法利用7,12二甲基苯并蒽(DMBA)作为始动剂,无机砷主要甲基化代谢产物DMA(V)进一步还原代谢生成的二甲基次胂酸[DMA(Ⅲ)]作为促进剂的致小鼠皮肤肿瘤两阶段动物模型;观察肿瘤的发生数,通过高效液相色谱法(HPLC),测量小鼠皮肤中DNA氧化损伤的生物标志物8-氧-2′-脱氧鸟嘌呤核苷(8-oxodG)的变化。结果在致小鼠皮肤肿瘤动物模型中,背部皮肤局部连续涂抹DMA(Ⅲ),观察到皮肤肿瘤数及表皮组织8-oxodG的生成量明显增多(P<0.05)。结论无机砷甲基化代谢产物的促肿瘤发生作用与DMA(V)在体内进一步还原代谢生成的代谢产物DMA(Ⅲ)诱发的氧化应激密切相关。
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关 键 词: | 二甲基次胂酸 氧化应激 促肿瘤作用 皮肤肿瘤 |
Dimethylarsinous acid-promoted skin tumorigenesis through the induction of oxidative stress in mice |
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Abstract: | Objective To investigated the relationship between skin-tumor promotion and oxidative stress caused by dimethylated arsenic in mice.Methods The experimental animal model was used to examine the effect of dimethylated arsenic, a metabolite of DMA(V), dimethylarsinous acid(DMA(Ⅲ))in skin tumorigenesis in mice. The 8-oxo-2′-deoxyguanosine(8-oxodG)analysis of epidermis was based on the method of HPLC.Results When mice were topically treated with trivalent dimethylated arsenic (DMA(Ⅲ)), a further reductive metabolite of DMA(V), not only an increase in skin tumors but also an elevation of 8-oxodG in epidermis were observed.Conclusion These results suggest that tumor promotion due to DMA(V) administration is mediated by DMA(Ⅲ) through the induction of oxidative stress. |
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Keywords: | dimethylarsinous acid oxidative stress tumor promotion skin tumorigenesis |
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