氯雷他嗪衍生的烷基化物质产生的DNA链间交联对白血病细胞系的致死性。
Lethality to leukemia cell lines of DNA interstrand cross-links generated by Cloretazine derived alkylating species.
作者信息
Penketh Philip G, Baumann Raymond P, Ishiguro Kimiko, Shyam Krishnamurthy, Seow Helen A, Sartorelli Alan C
机构信息
Department of Pharmacology and Developmental Therapeutics Program, Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
出版信息
Leuk Res. 2008 Oct;32(10):1546-53. doi: 10.1016/j.leukres.2008.03.005. Epub 2008 May 13.
Abstract
Cloretazine [1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine; VNP40101M; 101M] is a relatively new prodrug with activity in elderly acute myelogenous leukemia (AML) patients. Its therapeutic action is due largely to the production of 1-(3-cytosinyl),2-(1-guanyl)ethane cross-links (G-C ethane cross-links) in DNA. The numbers of cross-links produced in three experimental leukemia lines (L1210, U937 and HL-60) were fewer than 10 per genome at their respective LC50 concentrations. Only 1 in approximately 20,000 90CE molecules produces a cross-link in the AGT (O6-alkylguanine-DNA alkyltransferase) negative L1210 and U937 cell lines and 1 in 400,000 in the AGT positive HL-60 cell line.
摘要
氯雷他嗪[1,2 - 双(甲基磺酰基)-1-(2 - 氯乙基)-2 - [(甲氨基)羰基]肼；VNP40101M；101M]是一种相对较新的前体药物，对老年急性髓性白血病(AML)患者具有活性。其治疗作用主要归因于在DNA中产生1-(3 - 胞嘧啶基)，2-(1 - 鸟嘌呤基)乙烷交联(G - C乙烷交联)。在三种实验性白血病细胞系(L1210、U937和HL - 60)中，在各自的半数致死浓度(LC50)下，每个基因组产生的交联数少于10个。在AGT( O6 - 烷基鸟嘌呤 - DNA烷基转移酶)阴性的L1210和U937细胞系中，大约20,000个90CE分子中只有1个产生交联，而在AGT阳性的HL - 60细胞系中，400,000个分子中才有1个产生交联。
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