Deoxyribonucleic acid crosslinking by 4-hydroperoxycyclophosphamide in cyclophosphamide-sensitive and -resistant L1210 cells.

Deoxyribonucleic acid crosslinking by 4-hydroperoxycyclophosphamide in cyclophosphamide-sensitive and -resistant L1210 cells.
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环磷酰胺敏感和耐药的 L1210 细胞中 4-氢过氧环磷酰胺的脱氧核糖核酸交联。

DOI:
10.1016/0006-2952(84)90541-0
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发表时间:
1984
影响因子:
5.8
通讯作者:
Hilton,J
Hilton,J
中科院分区:
医学2区
文献类型:
--
作者:
Hilton,J

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4-氢过氧环磷酰胺是环磷酰胺的一种合成活化形式,已用于研究对环磷酰胺敏感和耐药的L1210细胞系中的DNA交联。交联出现的时间过程和链间与DNA-蛋白质交联的比例支持磷酰胺氮芥是来自环磷酰胺的最终烷化剂的信念。细胞存活率和DNA交联的研究与环磷酰胺耐药的L1210细胞系表明,电阻与失败的4-氢过氧环磷酰胺产生DNA交联。通过将耐药细胞暴露于双硫仑来逆转这种情况的能力指出了醛脱氢酶在环磷酰胺耐药机制中的作用。
4-Hydroperoxycyclophosphamide, a synthetic, activated form of cyclophosphamide, has been used to study DNA crosslinking in L1210 cell lines sensitive and resistant to cyclophosphamide. The time course of crosslink appearance and the proportion of inter-strand to DNA-protein crosslinks support the belief that phosphoramide mustard is the ultimate alkylating agent derived from cyclophosphamide. Cell survival and DNA crosslinking studies with a cyclophosphamide-resistant L1210 cell line indicate that resistance is associated with a failure of 4-hydroperoxycyclophosphamide to produce DNA crosslinks. The ability to reverse this situation by exposure of resistant cells to disulfiram points to a role of aldehyde dehydrogenase in this mechanism of cyclophosphamide resistance.
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