DNA damage and sequence specificity of DNA binding of the new anti-cancer agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate)
| Autor: | Kw Kohn, Massimo Broggini, W. B. Mattes, Maurizio D'Incalci, Mauro Ponti, Ja Hartley |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Bridged-Ring Compounds
Cancer Research Tertiary amine Cell Survival DNA damage Guanine Stereochemistry Antineoplastic Agents Alkylation Bridged Bicyclo Compounds chemistry.chemical_compound Tumor Cells Cultured Animals Humans Leukemia L1210 Interphase Base Sequence Dose-Response Relationship Drug Bicyclic molecule Chemistry DNA Neoplasm Cell cycle Bridged Bicyclo Compounds Heterocyclic In vitro Oncology Biochemistry DNA DNA Damage Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.1990.53 |
| Popis: | The DNA damage and the sequence specificity of guanine-N7 alkylation produced by the novel, positively charged, antineoplastic agent 1,4-bis(2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis maleate) and its uncharged tertiary amine analogue 1,4-bis(2'-chloroethyl)-1,4-diazacyclohexane (Dabis analogue) were investigated in L1210 cells and isolated DNA. Both compounds are cytotoxic in vitro causing an arrest of L1210 cells in G2/M phase of the cell cycle. In isolated DNA, Dabis maleate alkylates guanine at the N7-position with some differences in specificity compared to other alkylating agents (e.g. nitrogen mustard). Significant differences are also evident between Dabis maleate and Dabis analogue, suggesting that Dabis analogue is not the sole alkylating species of Dabis maleate. Using the alkaline elution technique a moderate number of DNA interstrand cross-links were detected in L1210 cells treated with both compounds, which were completely repaired within 24 h. Dabis maleate and Dabis analogue do not cause DNA single strand breaks or DNA protein cross-links at the doses at which DNA interstrand cross-links were detected. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|