Fused pyrazine mono-N-oxides as bioreductive drugs III. Characterization of RB 90740 in vitro and in vivo
| Autor: | S. Cole, N Robertson, Gerald E. Adams, Dietmar W. Siemann, Terence Jenner, Stephens Ma, Ian J. Stratford, Angela Haigh, Matthew A. Naylor |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Cancer Research Pyrazine Cell Survival Antineoplastic Agents Mice chemistry.chemical_compound In vivo Cricetinae Tumor Cells Cultured Animals Cytotoxic T cell Pharmacology (medical) Pharmacology Mice Inbred C3H Chemistry Neoplasms Experimental Molecular biology In vitro Cell killing Oncology Pyrazines Toxicity Female Lead compound DNA DNA Damage |
| Zdroj: | Anti-Cancer Drugs. 6:259-269 |
| ISSN: | 0959-4973 |
| DOI: | 10.1097/00001813-199504000-00010 |
| Popis: | RB 90740 is the lead compound in a series of aromatic mono-N-oxide bioreductive drugs. The compound shows considerably greater toxicity towards hypoxic verses aerobic mammalian cells in vitro. The differential in concentration required to give the same level of cell killing under these conditions ranges from 3.5 in a human bronchio-alveolar tumor cell line up to 120 in a rodent cell line defective in the repair of DNA strand breaks. The ability of RB 90740 to cause DNA strand breaks under hypoxic conditions was confirmed by alkaline sucrose gradient and pulsed field gel electrophoresis techniques. Despite these properties demonstrated in vitro, RB 90740 was shown not to be cytotoxic to hypoxic cells in experimental murine tumors in vivo. This may be due, in part, to the level of hypoxia (< 0.02% O2) necessary to produce toxicity in vitro. |
| Databáze: | OpenAIRE |
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