甲氨蝶呤治疗类风湿关节炎对外周血淋巴细胞DNA的损伤

目的研究多次低剂量应用甲氨蝶呤治疗类风湿关节炎(RA)病人造成的淋巴细胞DNA的损伤,并探讨四氢叶酸对该损伤的保护作用。方法应用甲氨蝶呤10mg/次,每周1次,共8周,同时在应用甲氨蝶呤4h后应用相同剂量的甲酰四氢叶酸;用单细胞凝胶电泳方法检测其外周血淋巴细胞DNA的损伤及修复情况。结果单用甲氨蝶呤组细胞尾长及拖尾频率与对照组相比差异均有显著性,而同时应用等量的甲酰四氢叶酸其细胞尾长及拖尾频率与对照组相比差异无显著性。结论单细胞凝胶电泳技术可敏感地检测RA病人多次应用低剂量甲氨蝶呤造成的外周血淋巴细胞DNA损伤,并能反映甲酰四氢叶酸对甲氨蝶呤所致的DNA损伤的保护作用,为探讨甲氨蝶呤治疗RA引起的不良反应机制提供了线索。

Low-dosed methotrexate treating rheumatoid arthritis causes peripheral lymphocytic DNA damage

Objective To study DNA lesion in peripheral lymphocytes caused by low-dosed methotrexate (MTX) , and discuss the protective action of folinic acid. Method Thirty patients with rheumatoid arthritis (RA) on a 10 mg weekly dosage of MTX, i.m., for eight weeks, were given the same dosage of folinic acid as a single dose 4 hours after MTX administration, i.m.. Comet assay (SCGE) was used to evaluate the DNA lesion for each patient. Results MTX produced a significant DNA injury in peripheral lymphocytes as proved by the increased tail length and frequency of cell tailing in group 2. Inversely, folinic acid produced a significant protection against DNA injury induced by MTX in group 3. Conclusion SCGE can detect DNA damage caused by low-dosed MTX, and can reflect the protective effect of folinic acid sensitively. This data may provide a clue to monitoring the sensitivity and genotoxicity during the MTX treatment of RA.