三氧化二砷对小鼠脑神经元DNA损伤作用

DNA damage in brain of mice exposed to arsenic trioxide

关键词:  三氧化二砷  脑组织  8-羟基-2’-脱氧鸟嘌呤核苷  单细胞凝胶电泳试验  神经毒性

Key words:  As₂O₃  brain tissue  8-hydroxy-2’-desoxyguanosine  single cell gel  electrophoresis  neurotoxicity

摘要:

［目的］ 为探讨砷的中枢神经系统毒性作用机制提供实验依据。［方法］昆明种小鼠40只，随机分为4组：1、2、4 ppm三氧化二砷染毒组和生理盐水组。连续染毒60 d，取大脑，用免疫组化方法观察脑皮质神经细胞8-羟基-2’-脱氧鸟嘌呤核苷（8-OH-dG）的表达，并用单细胞凝胶电泳试验检测脑神经元的单链DNA断裂程度。［结果］各染砷组小鼠脑皮质神经细胞出现肿胀、胞质内有空泡变性、核固缩、碎裂等病理学变化，神经组织中8-OH-dG呈现明显的高表达，而且神经细胞可见明显的彗尾、且随砷暴露剂量增高其彗尾变长。［结论］慢性低剂量砷暴露可诱发小鼠神经元的DNA损伤，脑皮质神经元可能是砷神经毒性作用的主要靶细胞。

Abstract:

［Objective］To provide evidences for exploring the mechanism of arsenic (As) toxicity to central nervous system.［Methods］Forty mice were divided into 4 groups, e.g., one control and 3 experimental groups (1ppm As₂O₃，2 ppm As₂O₃，4 ppm As₂O₃). As₂O₃ was administered ad libitum in water for 60 days. Immunohistochemistry method was used to observe 8-hydroxy-2’-desoxyguanosine (8-OH-dG) expression in brain neurons of mice. Single cell gel electrophoresis method was used to examine the DNA breakage levels in these neurons of mice.［Results］The degenerative and necrotic pathological changes and stronger expression of 8-OH-dG were observed in the brain cortex of mice exposed to As. There were obvious comet tails in brain neurons of mice exposed to As, and the comet tail distances were increasing as the concentration of As increasing.［Conclusions］DNA damage of cortex neurons in mice was induced by arsenic in low dose, and cortex neurons mightbe main target of the arsenic neurotoxicity.