用彗星实验技术分析MTX对小鼠细胞DNA的损伤作用

Detection of DNA Damage Induced by MTX in Mouse Cells ( spleen,bone marrow,thymus and peripheral lymphocytes) Using the Comet Assay

MTX是一种抗叶酸药物 ,作用于增殖细胞 ,为了解其作用机制和探测其遗传毒性靶器官 ,以小鼠为研究对象 ,用彗星实验技术检测了MTX腹腔注射染毒后对脾、骨髓、胸腺、和外周血淋巴细胞的DNA损伤作用及其与MTX剂量间的相关。 1.2 5～ 5mg/kgMTX可诱发小鼠体内 4种细胞的DNA单链断裂 ,核DNA损伤程度与用药剂量呈正相关。不同种类细胞对MTX的易感性不同 ,脾、骨髓、胸腺、外周血淋巴细胞可能是MTX的遗传毒性靶细胞。

To understand the mechanism of MTX further and to investigate the genotoxic target organs. DNA damage and the correlation with dose of MTX were studied by using the alkaline single cell gel electrophoresis (comet assay. ). The results showed that: Significant increase in DNA migration and comet frequency in the spleen, thymus, bone marrow and peripheral lymphocytes of the mice were induced after intraperitoneal treatment of MTX at a dose of 1.25～5mg/kg .The migration of nuclear DNA and comet frequency of spleen, thymus, bone marrow and peripheral lymphocytes in the dose-response study showed a dose-dependent increase. There are difference in sensitivity of various organs in the mice and cells of spleen, thymus, bone marrow and peripheral lymphocytes may be the important target cells of MTX.The comet tail of peripheral lymphocytes in suitable as a biomarker for reflecting the sensitivity of organs after treatment of MTX.