Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA da(双硫仑是一种直接的和强有力的人类O6-甲基鸟嘌呤-DNA甲基转移酶抑制剂(MGMT)在脑肿瘤细胞和小鼠大脑和DN).PDFVIP
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Carcinogenesis vol.35 no.3 pp.692–702, 2014
doi:10.1093/carcin/bgt366
Advance Access publication November 5, 2013
6
Disulfiram is a direct and potent inhibitor of human O -methylguanine-DNA
methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly
increases the alkylating DNA damage
1,2 2,3 4 so that the guanine in the DNA is simply restored in an error-free
Ameya Paranjpe , Ruiwen Zhang , Francis Ali-Osman ,
5 1,2, direct reversal reaction (2). Because, the alkyl group is covalently
George C.Bobustuc and Kalkunte S.Srivenugopal *
bound to the protein, MGMT is functionally inactivated after each
1Department of Biomedical Sciences and 2Cancer Biology Center, and reaction, and the inactive protein is degraded through the ubiquitin
3Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech (ub) proteolytic pathway (4). MGMT is abundantly expressed in liver
University Health Sciences Center, Amarillo, TX 79106, USA, 4Department
and other normal tissues, but is present at very low levels in the bone
of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University,
5 marrow and normal brain (5). The repair function of MGMT is essen-
Durham, NC 27710, USA and Neuro-Oncology Section, Aurora Advanced
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