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Differential inactivation of O6-methylguanine-dna methyltransferase activity by O6-arylmethylguanines

✍ Scribed by Katsuyoshi Mineura; Masahito Fukuchi; Masayoshi Kowada; Isamu Terashima; Kohfuku Kohda

Publisher
John Wiley and Sons
Year
1995
Tongue
French
Weight
473 KB
Volume
63
Category
Article
ISSN
0020-7136

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✦ Synopsis

Activity of 06-methylguanine-DNA methyltransferase (MGMT) is well related with drug resistance of tumor cells to chloroethylnitrosoureas (CENUs), because MGMT removes CENU-induced O6-alkyIguanines in DNA by accepting the alkyl group at a cysteine moiety. Inactivation of MGMT is a feasible way to overcome MGMT-related resistance of tumor cells to CENUs. 06-Benzylguanine is known to be a strong depleter of MGMT. We previously reported the potentiation effect of 06-arylmethylguanine derivatives on cytotoxicity of I -(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitro~urea hydrochloride (ACNU), a CENU, for HeLa S3 cells. In this study,

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