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Title: Intracellular localization and intercellular heterogeneity of the human DNA repair protein O6-methylguanine-DNA methyltransferase
Authors: Belanich, M.
Randall, T.
Pastor, M.A.
Kibitel, J.T.
Alas, L.G.
Dolan, M.E.
Schold Jr., S.C.
Gander, M.
Lejeune, F.J.
Li, B.F.L. 
White, A.B.
Wasserman, P.
Citron, M.L.
Yarosh, D.B.
Keywords: 1,3-Bis(2-chlorethyl)-1-nitrosourea
Issue Date: 1996
Citation: Belanich, M., Randall, T., Pastor, M.A., Kibitel, J.T., Alas, L.G., Dolan, M.E., Schold Jr., S.C., Gander, M., Lejeune, F.J., Li, B.F.L., White, A.B., Wasserman, P., Citron, M.L., Yarosh, D.B. (1996). Intracellular localization and intercellular heterogeneity of the human DNA repair protein O6-methylguanine-DNA methyltransferase. Cancer Chemotherapy and Pharmacology 37 (6) : 547-555. ScholarBank@NUS Repository.
Abstract: O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl adducts from DNA and may be important in tumor resistance to alkylation chemotherapy. MGMT was visualized in human cells and tumor tissues with monoclonal antibodies against MGMT and immunofluorescence microscopy, and fluorescent signals were quantified by digital image analysis. MGMT was found both in the cytoplasm and the nucleus, and in either locale the protein reacts with alkylated DNA bases and becomes inactivated and lost from the cell. Cell lines in culture and xenografts showed a broad normal distribution of nuclear MGMT levels, but human brain tumors often showed a skewed distribution, with a significant fraction of cells with high levels of MGMT. O6-Benzylguanine, a suicide substrate inactivator for MGMT activity, reduced MGMT in human cells and in a mouse xenograft to levels undetectable by antibody assay 1 h post-treatment. In melanoma specimens taken from a patient 3 h post-treatment with temozolomide, MGMT levels were reduced by 70%. This quantitative immunofluorescence assay can be used to monitor MGMT and its depletion in human tumors to improve the use of alkylating agents in cancer chemotherapy.
Source Title: Cancer Chemotherapy and Pharmacology
ISSN: 03445704
DOI: 10.1007/s002800050427
Appears in Collections:Staff Publications

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