二甲基次胂酸促小鼠皮肤肿瘤发生与诱发氧化应激

Dimethylarsinous acid-promoted skin tumorigenesis through the induction of oxidative stress in mice

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。

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.