DNA alkylation and interstrand cross-linking by treosulfan.
DNA alkylation and interstrand cross-linking by treosulfan.
复制标题
Treosulfan的DNA烷基化和链间交联。
DOI：
10.1038/sj.bjc.6690043
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发表时间：
1999-01
影响因子：
8.8
通讯作者：
Baumgart, J
中科院分区：
文献类型：
--
作者：
Hartley, J A;O'Hare, C C;Baumgart, J
抗肿瘤药物treosulfan （l -苏糖醇1,4-二甲基磺酸，Ovastat）是在生理条件下通过相应的单环氧化合物非酶转化为l -二氧基丁烷的环氧化合物的前药。目前的研究支持这样的假设，即在体外细胞毒性需要曲硫丹的这种转化。脱氧核糖核酸烷基化和质粒DNA链间交联在曲硫丹处理后被观察到，但这再次通过环氧化物物种产生。烷基化发生在鸟嘌呤碱基上，其序列选择性与其他烷基化剂（如氮芥）相似。在treosulan处理的K562细胞中，交联形成缓慢，在大约24小时达到峰值。用预先形成的环氧化物孵育K562细胞显示出更快和更有效的DNA交联。©1999癌症研究运动
The anti-tumour drug treosulfan (L-threitol 1,4-bismethanesulphonate, Ovastat) is a prodrug for epoxy compounds by converting non-enzymatically to L-diepoxybutane via the corresponding monoepoxide under physiological conditions. The present study supports the hypothesis that this conversion of treosulfan is required for cytotoxicity in vitro. DNA alkylation and interstrand cross-linking of plasmid DNA is observed after treosulfan treatment, but this is again produced via the epoxide species. Alkylation occurs at guanine bases with a sequence selectivity similar to other alkylating agents such as the nitrogen mustards. In treosulfan-treated K562 cells, cross-links form slowly, reaching a peak at approximately 24 h. Incubation of K562 cells with preformed epoxides shows faster and more efficient DNA cross-linking. © 1999 Cancer Research Campaign