Mechanisms of hypoxic cell radiosensitization and the development of new sensitizers.
Some of the mechanisms by which drugs can potentiate the radiation response of tumors and cells in culture are discussed. Emphasis is placed on the action of nitroaromatic and heterocyclic compounds as hypoxic cell radiosensitizers, and some potential successors to misonidazole (MISO) are described. These include desmethylmisonidazole and SR 2508, selected because of their low toxicity in experimental systems. Groups of compounds, more efficient sensitizers than would be predicted from electron affinity correlations, have been examined and the use of Ro-03-8799 or RSU 1047 is proposed. Finally, ortho-substituted nitroimidazoles and electron-affinic compounds with alkylating groups are described. The latter group, in particular, holds promise for the development of compounds much superior to MISO.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D005609:Free Radicals; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D009593:Nitroimidazoles / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000494:pharmacology*
D005609:Free Radicals; D007093:Imidazoles; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents