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细菌和哺乳动物的3-甲基腺嘌呤-DNA糖基化酶对氮芥DNA加合物的切除作用

Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases.

作者信息

Mattes W B, Lee C S, Laval J, O'Connor T R

机构信息

Groupe Réparation des lesions radio- et chimioinduites, CNRS URA147, Institut Gustave-Roussy, Villejuif, France.

出版信息

Carcinogenesis. 1996 Apr;17(4):643-8. doi: 10.1093/carcin/17.4.643.

DOI:10.1093/carcin/17.4.643
PMID:8625472
Abstract

Nitrogen mustards are among the DNA alkylating agents most widely used in chemotherapy. The homogeneous Escherichia coli AlkA protein (3-methyladenine-DNA glycosylase II) is shown to excise damaged guanine and adenine bases from DNA modified by mechlorethamine, uracil mustard, phenylalanine mustard and chlorambucil, and less efficiently acridine mustard adducts. Homogeneous recombinant human and rat 3-methyladenine-DNA glycosylases excise adducts formed by nitrogen mustards less efficiently than the AlkA protein. In addition to the in vitro excision of adducts, the AlkA protein eliminates cytotoxic mechlorethamine adducts from DNA in vivo.

摘要

氮芥是化疗中使用最广泛的DNA烷基化剂之一。已表明，纯的大肠杆菌AlkA蛋白（3-甲基腺嘌呤-DNA糖基化酶II）能从经氮芥、尿嘧啶氮芥、苯丙氨酸氮芥和苯丁酸氮芥修饰的DNA中切除受损的鸟嘌呤和腺嘌呤碱基，对吖啶氮芥加合物的切除效率较低。纯的重组人及大鼠3-甲基腺嘌呤-DNA糖基化酶切除氮芥形成的加合物的效率低于AlkA蛋白。除了在体外切除加合物外，AlkA蛋白还能在体内消除DNA中的细胞毒性氮芥加合物。

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