摘要
目的观察不同价态、不同剂量砷染毒大鼠肝脏中DNA甲基转移酶和砷甲基转移酶mRNA的表达情况,寻找两者间的相关性及不同价态砷(iAs3+和iAs5+)体内甲基化间的差异。方法将35只健康清洁级Wistar雄性大鼠按体重随机分为7组,分别为正常对照(去离子水)组和低剂量(1/45 LD50,2.33 mg/kg)、中剂量(1/15 LD50,6.67 mg/kg)、高剂量(1/5LD50,20.00 mg/kg)砷酸氢钠(iAs5+)染毒组以及低剂量(2.33 mg/kg)、中剂量(6.67 mg/kg)、高剂量(20.00 mg/kg)亚砷酸钠(iAs3+)组,每组5只。采用自由饮水方式进行染毒,连续染毒90 d。采用实时荧光定量PCR法测定肝脏中DNA甲基转移酶(DNMT1、DNMT3A、DNMT3B)和砷甲基转移酶(As3MT)mRNA的表达情况。结果与对照组相比,各染毒组大鼠肝脏中As3MT mRNA的表达量较高,DNMT3A、DNMT3B mRNA的表达量较低,高、低剂量亚砷酸钠染毒组和高剂量砷酸氢钠染毒组DNMT1 mRNA的表达量均较高,中剂量亚砷酸钠染毒组和低剂量砷酸氢钠染毒组DNMT1 mRNA的表达量均较低,差异有统计学意义(P<0.05)。随着亚砷酸钠染毒剂量的升高,大鼠肝脏中As3MT mRNA的表达量呈上升趋势,DNMT3A、DNMT3B mRNA的表达量呈下降趋势;随着砷酸氢钠染毒剂量的升高,大鼠肝脏中As3MT mRNA的表达量呈下降趋势,DNMT3A、DNMT3B、DNMT1 mRNA的表达量呈上升趋势。As3MT的表达量与DNMT3A和DNMT3B表达量呈负相关(P<0.01);与DNMT1表达量无相关关系(P>0.01)。结论长期亚慢性暴露iAs3+和iAs5+均可促进As3MT的表达,抑制DNMT3A及DNMT3B的表达,但iAs3+和iAs5+间在剂量-效应关系上呈反向性;机体As3MT表达上调与DNMT3A和DNMT3B表达抑制间具有协同效应,并可导致基因低甲基化。
Objective To investigate the influence on arsenic methyhransferase （As3MT） and DNA methyltransferase （DNMTI, DNMT3A, DNMT3B） mRNA expression in rats liver treated with sodium arsenite and sodium arsenate and seek for the difference of DNA and arsenic methylation and both＇s correlation between sodium arsenite and sodium arsenate（iAs3＋ and iAs5＋）. Methods Different valence state and doses of arsenic were administrated through drinking water to Wistar rats, male rats were divided into seven group randomly,five in each group, control group （deionized water）, sodium arsenite low dose group （1/45 LD50,2.33 mg/kg）,moderate dose group （1/15 LD50,6.67 mg/kg）,high dose group （1/5 LD50,20.00 mg/kg） administrated with different concentrations of sodium arsenite; sodium arsenate low dose group （1/45 LD50,2.33 mg/kg）, moderate dose group （1/15 LD50,6.67 mg/kg）,high dose group （1/5 LD50,20.00 mg/kg） administrated with different concentrations of sodium arsenate. The reagents were given through drinking water, for 90 consecutive days. At the end of the third month, the rats were sacrificed to collect the liver,and the expression of DNA and arsenic methyltransferase were detected by real-time PCR in liver genome mRNA. Results The difference of As3MT and DNA methyltransferase mRNA expression in every group was significant （P〈0.05） compared with the control group; the expression of As3MT mRNA increased and the expression of DNMT3A and DNMT3B mRNA were decreased in arsenic the exposed group; the expression of DNMT1 mRNA increased in high and low iAs3＋ exposed group and in high iAs5＋ exposed group,the expression of DNMT1 mRNA decreased in moderate iAs3＋ exposed group and in low iAs5＋ exposed group. With the increasing dose of iAs3＋, As3MT mRNA expression showed an increasing trend and DNMT3A and DNMT3B mRNA expression showed a decresing trend in iAs3＋ group; with the increase of iAs5＋ dose, As3MT mRNA expression showed a decreasing trend and DNMT3A, DNMT3B and DNMT1 mR
出处
《环境与健康杂志》
CAS
CSCD
北大核心
2012年第1期20-25,共6页
Journal of Environment and Health
基金
国家自然科学基金(30960323)
新疆自治区高校科研计划重点项目(XJEDU2011I27)
新疆医科大学科研创新基金(XJC201017)
关键词
亚砷酸钠
砷酸氢钠
砷甲基转移酶
DNA甲基转移酶
甲基化
Sodium arsenite
Sodium arsenate
Arsenic methyltransferases
DNA methyltransferases
Methylation
