血液肿瘤细胞对氧化砷的敏感性与其抗氧化能力的关系

目的　探讨血液肿瘤细胞对三氧化二砷 (As2 O3 )的敏感性和细胞抗氧化能力的关系。方法　应用 9个血液肿瘤细胞系 ,通过细胞活力、形态学和流式细胞仪检测细胞凋亡 ,并测定细胞系的谷胱甘肽 (GSH)含量和 4种抗氧化酶的活性。结果　除了HL 6 0、U937、K5 6 2和Jurkat细胞外 ,其他5个细胞对As2 O3 诱导的凋亡敏感。与敏感细胞系比较 ,As2 O3 耐受细胞系存在较高的GSH含量和(或 )过氧化氢酶活性。谷胱甘肽过氧化物酶、谷胱甘肽S转移酶和超氧化物歧化酶活性与细胞对As2 O3 诱导凋亡效应敏感性无明显相关。结论　细胞内GSH水平和过氧化氢酶的活性是决定血液肿瘤细胞对As2 O3 敏感性的重要因素。

The relationship between sensitivity to arsenic trioxide and antioxidative capacity of malignant hematopoietic cells

Objective To detect the relationship between sensitivity of malignant hematopoietic cells to arsenic trioxide (As 2O 3) and cellular capacity against oxidation.Methods Nine cell lines derived from hematopoietic malignancies were treated with As 2O 3 in vitro. Apoptosis was assessed by cellular viability, cytomorphology and flow cytometry. The As 2O 3 treated cells were examined for glutathione (GSH) level and activity of catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST) and glutathione peroxidase (GPX).Results Of the 9 cell lines examined, the acute promyelocytic leukemia cell line NB 4 and its retinoic acid resistant subclones R 2 and MR 2, the Burkitt lymphoma cell line Namalwa and multiple myeloma cell line RPMI 8226 were sensitive to As 2O 3 induced apoptosis while the acute T cell leukemia cell line (Jurkat) and 3 cell lines (HL 60, U937, K562) of myelogenous leukemia origin were not. In comparison with the sensitive cell lines, higher activity of CAT was found in HL 60 and U937, higher level of GSH in Jurkat, and both in K562. However, activity of GPX, GST and SOD did not significantly correlate with their resistance to As 2O 3 induced apoptosis.Conclusion Intracellular GSH level and/or catalase activity are important factors to determine sensitivity of malignant hematopoietic cells to As 2O 3 induced apoptosis.