氧氮磷杂环化合物对U937细胞DNA断裂的诱导作用。

Induction of DNA breakage in U937 cells by oxazaphosphorines.

作者信息

Mazur Lidia, Opydo-Chanek Małgorzata, Stojak Marta, Baran Jarosław, Niemeyer Ulf

机构信息

Department of Experimental Hematology, Jagiellonian University, R. Ingardena 6, 30-060 Kraków, Poland.

出版信息

Folia Biol (Krakow). 2010;58(1-2):15-20. doi: 10.3409/fb58_1-2.15-20.

DOI:10.3409/fb58_1-2.15-20

PMID:20420190

Abstract

Oxazaphosphorines are a class of DNA alkylating agents. The aim of the present study was to compare the possible influence of three new generation oxazaphosphorines, D-17272 (mafosfamide cyclohexylamine salt), D-18864 (4-hydro-peroxy-cyclophosphamide), and D-19575 (glufosfamide, beta-D-glucose-isophosphoramide mustard) on DNA damage induction in the human histiocytic lymphoma U937 cells. The flow cytometry APO-BRDU assay, based on the TUNEL method, was used for the in situ detection of DNA strand breaks. After exposure of U937 cells to the oxazaphosphorines, the patterns of temporary changes in the frequency of TUNEL positive U937 cells, expressing DNA breakage, were determined. The effects of the oxazaphosphorines on U937 cells were dependent on the agent tested and its dose, and the time intervals after the drug application. The different potential of D-17272, D-18864 and D-19575 to induce DNA strand breakage in the human histiocytic lymphoma U937 cells was shown.

摘要

氧氮磷杂环类化合物是一类DNA烷化剂。本研究的目的是比较三种新一代氧氮磷杂环类化合物，即D-17272（马法兰环己胺盐）、D-18864（4-氢过氧环磷酰胺）和D-19575（葡磷酰胺，β-D-葡萄糖异磷酰胺氮芥）对人组织细胞淋巴瘤U937细胞DNA损伤诱导的可能影响。基于TUNEL法的流式细胞术APO-BRDU检测用于原位检测DNA链断裂。将U937细胞暴露于氧氮磷杂环类化合物后，确定表达DNA断裂的TUNEL阳性U937细胞频率的临时变化模式。氧氮磷杂环类化合物对U937细胞的影响取决于所测试的药物及其剂量，以及给药后的时间间隔。结果显示了D-17272、D-18864和D-19575在人组织细胞淋巴瘤U937细胞中诱导DNA链断裂的不同潜力。