Novogrodsky A, Dvir A, Ravid A, Shkolnik T, Stenzel K H, Rubin A L, Zaizov R
Cancer. 1983 Jan 1;51(1):9-14. doi: 10.1002/1097-0142(19830101)51:1<9::aid-cncr2820510104>3.0.co;2-4.
Polar organic compounds, such as dimethylsulfoxide and butyric acid, are known to induce differentiation in Friend erythroleukemia cells as well as in other cell types. It has been found that many of the compounds that induce cellular differentiation, inhibit 3H-thymidine incorporation and induce cell damage when incubated with leukemic cells from patients with acute or chronic myelogenous or acute lymphocytic leukemia. These effects are time and dose dependent. Among the compounds tested, butyrate was the most potent. Parenteral administration of butyrate (500 mg/kg/day) for ten days to a child with acute myelogenous leukemia in relapse, and resistant to conventional therapy, resulted in elimination of myeloblasts from the peripheral blood, an increase in mature myeloid cells and a reduction in 3H-thymidine uptake by the patient's peripheral blood cells. Bone marrow myeloblasts were reduced from 70-80% to 20% following the course of intravenous butyrate. No impairment of liver or renal function and no coagulation abnormalities were observed during butyrate treatment. Organic agents that induce cell differentiation may provide additional reagents for the clinical management of selected cases of leukemia.
极性有机化合物,如二甲基亚砜和丁酸,已知可诱导Friend红白血病细胞以及其他细胞类型发生分化。已发现,许多诱导细胞分化的化合物,在与急性或慢性粒细胞性白血病或急性淋巴细胞性白血病患者的白血病细胞一起孵育时,会抑制3H-胸腺嘧啶核苷掺入并诱导细胞损伤。这些作用具有时间和剂量依赖性。在所测试的化合物中,丁酸盐最为有效。对一名复发且对传统疗法耐药的急性粒细胞性白血病患儿进行为期十天的丁酸盐肠胃外给药(500毫克/千克/天),导致外周血中原始粒细胞消失,成熟髓细胞增加,且患者外周血细胞对3H-胸腺嘧啶核苷的摄取减少。静脉注射丁酸盐疗程结束后,骨髓原始粒细胞从70%-80%降至20%。在丁酸盐治疗期间,未观察到肝功能或肾功能损害以及凝血异常。诱导细胞分化的有机药物可能为某些白血病病例的临床治疗提供额外的试剂。