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背景与目的:为进一步了解甲氨蝶呤(Methotrexate,MTX)的作用机制,探测其对不同组织器官作用的敏感性。材料与方法:用单细胞凝胶电泳技术(Singlecellgelelectrophoresisassay,SCGE)检测小鼠腹腔注射MTX染毒1、3、6、12、24h后对肝、脾、骨髓、胸腺、肾、睾丸、胃和外周血淋巴细胞的DNA损伤作用及其与MTX剂量间的关系。结果:腹腔注射1.25~5mg/kgMTX可诱发小鼠脾细胞、骨髓细胞、胸腺细胞和外周血淋巴细胞的DNA单链断裂;核DNA损伤程度与用药剂量呈正相关。结论:MTX可致小鼠体内多脏器细胞的DNA单链断裂,不同脏器细胞对MTX的易感性不同,脾、骨髓、胸腺、外周血淋巴细胞可考虑为MTX的遗传毒性靶细胞。
BACKGROUND & AIM: To investigate the mechanism of action of methotrexate (MTX) and explore its sensitivity to different organs and tissues. MATERIALS AND METHODS: The cells of liver, spleen, bone marrow, thymus, kidney, testis, stomach and periphery were detected by single cell gel electrophoresis (SCGE) at 1,3,6,12 and 24 h after intraperitoneal injection of MTX Effect of DNA Damage on Hemocytes and Its Relationship with MTX Dose. Results: Intraperitoneal injection of 1.25 ~ 5mg / kg MTX induced DNA single strand breaks in splenocytes, bone marrow cells, thymocytes and peripheral blood lymphocytes. The degree of nuclear DNA damage was positively correlated with the dose of MTT. CONCLUSION: MTX can cause DNA single-strand breaks in multiple organ cells in mice. Different organs have different susceptibility to MTX. Spleen, bone marrow, thymus and peripheral blood lymphocytes can be considered as genotoxic target cells of MTX.