O6-Methylguanine-DNA Methyltransferase (O6-MT) Activity as an Index of Drug Responsiveness to Antitumor Chloroethylnitrosoureas in Xenografted Brain Tumors
The synthesized chloroethylnitrosoureas (CENUs), 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-α-D-glucopyranoside (MCNU), have been among the antitumor agents widely used for the treatment of malignant brain tumors . Methods for monitoring responsiveness of brain tumors to CENUs on the basis of a cell-killing mechanism have been needed to enhance therapeutic effectiveness. It is well documented that a DNA repair enzyme O6-methylguanine-DNA methyltransferase (O6-MT), identical to the term O6-alkylguanine-DNA alkyltransferase, eliminates the O6-methylguanine induced by CENUs and reflects the cellular resistance to CENUs in cultured cell strains and xenografted tumors [2–5]. Further in vivo work was warranted to establish a chemoserisitivity index of O6-MT activity. In the present paper, we test the relationship of O6-MT activity and responsiveness to CENUs in xenografted brain tumors.
KeywordsAntitumor Agent Crude Protein Extract Coop Treatment Maximum Inhibition Rate Xenografted Brain Tumor
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