Photo-enhancement of the mutagenicity of 9-anilinoacridine derivatives related to the antitumour agent amsacrine
| Autor: | Amira Pearson, Yoshihisa Iwamoto, Bruce C. Baguley, Lynnette R. Ferguson |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Amsacrine
Salmonella typhimurium Light Health Toxicology and Mutagenesis Acridine carboxamide Antineoplastic Agents Ames test Toxicology chemistry.chemical_compound Genetics medicine Frameshift Mutation Molecular Biology Proflavine Dose-Response Relationship Drug biology Aminoacridines Mutagenicity Tests food and beverages biology.organism_classification Binding constant Combinatorial chemistry Enterobacteriaceae chemistry Acridine Acridines Oxidation-Reduction DNA Mutagens medicine.drug |
| Zdroj: | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 268:35-41 |
| ISSN: | 0027-5107 |
| Popis: | The frameshift mutagenicity of the DNA intercalating drug proflavine is known to be enhanced by photoirradiation of bacterial cultures. To determine whether this phenomenon was also present in acridine-derived antitumour drugs, cultures of Salmonella typhimurium were exposed to the antileukaemia agent amsacrine and the experimental agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide dihydrochloride (acridine carboxamide) in the presence or absence of visible light. A small increase in mutagenicity was observed with amsacrine but not with acridine carboxamide. A series of analogues of amsacrine were then tested, and a striking relationship was found between the minimum drug concentration for mutagenicity and DNA binding affinity. In each case, photoirradiation was associated with a small increase in mutagenicity. Each of the compounds showing the photo-enhancement effect was capable of reversible one-electron oxidation. It is suggested that this oxidation occurs in bacteria, and that the DNA binding constant of the resulting acridine radical species will increase because of the extra positive charge. This increased DNA binding would be sufficient to explain the photo-enhancement of mutagenicity of these drugs. |
| Databáze: | OpenAIRE |
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