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作 者:庞文新[1] 王敏[1] 褚建新[1] 姜露[1] 赵钧铭[1]
机构地区:[1]中国医学科学院,中国协和医科大学血液学研究所,天津300020
出 处:《中国实验血液学杂志》1996年第4期399-402,共4页Journal of Experimental Hematology
摘 要:阿糖胞苷(Ara-C)是治疗急性粒细胞白血病的首选药物,但临床相当高比例的病人对Ara-C产生耐药性,致使化疗失败。因此,我们采用逐渐提高药量和连续传代的方法,建立了L615小鼠白血病体内Ara-C耐药模型(L615/Ara-C),最终耐药剂量稳定在150mg/kg。其生物学特性表现为L615/Ara-C小鼠经Ara-C治疗比L615小鼠经Ara-C治疗组存活时间明显缩短,流式细胞术检测证明G_0/G_1期细胞增加,S期细胞减少。有意义的是L615/Ara-C细胞对辐射的敏感性比L615细胞增高。1 - β- D - Arabinofuranosylcytosine (Ara - C) is a S - phase specific cytostatic agent and most commonly used in the treatment of acute myeloid leukemia (AML). Regimens containing Ara - C are highly effective and induce complete remission in a majority of treated patients. However, a high pro-portion of patients acquires resistance to the drug, rendering treatment schedules ineffective. There-fore, we established a modei in vivo for Ara - C resistance in L615 mouse leukmeia (named L615/ Ara- C), by increasing gradually the dosages of Ara - C and continuously propagating in L615 mice. Finally, the dosage of resistance to Ara - C reached 150 mg/kg. Present work described biological fea-tures of modei in vivo for Ara- C resistance to unravel mechanism(s) underlying Ara - C resistance. The biological features of L615/Ara - C were studied. It showed that the survival time of L615/ Ara- C mice treated with Ara - C was shorter than that of L615 mice obviously. The result of flow cytometry determination of L615/Ara - C celis revealed that the rate of G0/G1 phase cells was in-creased and the rate of S phase was decreased. The results partly explained the mechanism of Ara- C resistance. It was interesting to find the L615/Ara- C cells were more sensitive to radiation than that of L615 cells, it means irradiation could be used to treat patients with resistance to Ara- C.
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