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. 1991 Apr;2(2):185-9.
doi: 10.1097/00001813-199104000-00009.

O6-methylguanine as a modulator of antitumor activity of N-alkyl-N-nitrosoureas in vivo

L B Gorbacheva  1 , G V Kukushkina, S J Elksne, T D Miniker, Melnik SYa, M N Preobrazhenskaya
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O6-methylguanine as a modulator of antitumor activity of N-alkyl-N-nitrosoureas in vivo

L B Gorbacheva et al. Anticancer Drugs. 1991 Apr.

Abstract

The effect of O6-methylguanine (O6-MeG) on the therapeutic efficiency of 1-methyl-1-nitrosourea (MNU) and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) against the murine L1210 leukemia and B16 melanoma was studied in vivo. Although the level of O6-alkylguanine-DNA alkyltransferase (AGT) in L1210/BCNU leukemia cells was three times higher than in L1210 leukemia cells, no enhancement of the antitumor activity of MNU and BCNU in L1210 leukemia or B16 melanoma with O6-MeG or MNU potentiated markedly the cytotoxic effects of MNU and BCNU. Administration of O6-MeG to mice bearing L1210 leukemia led to delayed inhibition of DNA synthesis and appearance of long-term single-strand breaks in DNA of tumor cells.

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