亚砷酸钠致脏器细胞DNA链断裂的实验研究

Study on DNA Strand Breaks in Different Organs Induced by NaAsO_2

目的 观察不同剂量亚砷酸钠 (NaAsO2 )在不同时相引发小鼠体内细胞DNA链断裂损伤的影响。方法 采用单细胞凝胶电泳法 (SCGE)分别测定ICR小鼠皮下注射NaAsO2 0 .4 ,2 ,10mg/kg后 1,3,6h的脾脏、胸腺、骨髓和肝细胞的DNA链断裂损伤。结果 不同剂量亚砷酸钠注射后 ,可以发现 2和 10mg/kgNaAsO2 可诱发脾细胞、胸腺细胞、骨髓细胞DNA链断裂 ,各组出现的彗星细胞百分比明显高于对照组 ,同时DNA迁移距离也较对照组明显增大 ;而在染毒后不同时相观察的结果表明 ,NaAsO2 诱发脾细胞出现DNA链断裂损伤在 1h最为明显 ,而胸腺细胞和骨髓细胞相对较晚 ,DNA链断裂损伤高峰出现在染毒 3h ;染毒 6h ,各种组织细胞的DNA链断裂损伤开始减少 ,逐渐趋于正常。各剂量组及时间点均未观察到亚砷酸钠有诱导肝细胞DNA链断裂损伤的作用。结论 2mg/kg和 10mg/kgNaAsO2 可诱发小鼠体内脾、胸腺和骨髓细胞的DNA链断裂损伤 ,但不同细胞对NaAsO2

Objective To investigate DNA strand breaks induced by NaAsO 2 in different phases and different dosages in vivo.Methods Mice are treated through s.c. injection with NaAsO 2 at a dose of 0.4,2 and 10mg/kg.After injection mice are sacrificed at the end of 1,3 and 6 hours.DNA strand breaks are detected in the splenocyte,thymocyte,marrow cells and liver cells through SCGE(Single Cell Gel Electrophoresis).Results After different dosages treatment it is found that 2 and 10mg/kg NaAsO 2 could induce DNA damage not only in the frequency of comet cell but also in the migration of DNA breaks in cells from spleen,thymus and bone marrow.During the research of different time-course study,1 hour after NaAsO 2 treatment splenocyte appears DNA strand breaks most apparently.The peak of DNA strand breaks in thymocyte and marrow cell apperes 3 hours after treatment.After 6 hours treatment the DNA strand breaks fall down and accesse to normal level in different organs.NaAsO 2 induces DNA strand breaks in liver cell in our dosage and time scope.Conclusion Two mg/kg and 10mg/kg NaAsO 2 could induce DNA strand breaks in cells from spleen,thymus and bone marrow in vivo,but different cell type might have different reaction to NaAsO 2.