甲氨蝶呤对小鼠4种组织器官细胞DNA损伤作用

Detection of DNA damage induced by MTX in mouse organs(spleen, bone marrow,thymus and peripheral lymphocytes)

目的了解甲氨蝶呤(MTX)的作用机制,探测其作用的遗传毒性靶器官。方法用单细胞凝胶电泳技术检测了MTX染毒后脾、骨髓、胸腺和外周血淋巴细胞的DNA损伤情况及其与MTX剂量间的关系。结果腹腔注射1.25～5mg/kgMTX可诱发小鼠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关系。结论不同脏器细胞对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。外周血淋巴细胞在SCGE分析中的拖尾现象可作为用药后组织器官对药物敏感性反映的生物标志。

Objective To explore the mechanism of methatrexate（MTX） further and the genotoxic target organs, Method DNA damage and the correlation with dose of MTX were researched using alkaline single cell gel electrophoresis. Results Significant DNA damage in these cells of mice were induced after intraperitoneal treatment with MTX at a dose of 1.25-5 mg/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. Conclusion There is difference in sensitivity of various organs. Cells of spleen, thymus, bone marrow and peripheral lymphocytes may be the important target cells of MTX, The comet tail of peripheral lympbocytes is suitable as a biomarker for reflecting the sensitivity of organs after treatment with MTX.