1. O6-methylguanine as a modulator of antitumor activity of N-alkyl-N-nitrosoureas in vivo
- Author
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Elksne Sj, T. D. Miniker, Gorbacheva Lb, Melnik SYa, Preobrazhenskaya Mn, and Kukushkina Gv
- Subjects
Cancer Research ,Guanine ,Time Factors ,Drug Resistance ,chemistry.chemical_compound ,Mice ,In vivo ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Cytotoxic T cell ,Animals ,Pharmacology (medical) ,Drug Interactions ,Leukemia L1210 ,neoplasms ,Pharmacology ,Antitumor activity ,DNA synthesis ,O6-methylguanine ,Methylnitrosourea ,DNA, Neoplasm ,medicine.disease ,Carmustine ,Mice, Inbred C57BL ,Leukemia ,Oncology ,chemistry ,Mice, Inbred DBA ,Cancer research ,Nucleic Acid Conformation ,DNA ,Neoplasm Transplantation ,Alkyltransferase ,DNA Damage - 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.
- Published
- 1991