The nitroimidazoles have been found to selectively sensitize hypoxic cells to the effects of irradiation. The latest in this family of drugs is RO-07-0582, which is able to mimic 80% of the oxygen effect at a concentration of 5 mM by modifying the sensitivity of hypoxic cells to single doses of gamma rays; however, it is not a substitution for oxygen in promoting the repair of sublethal radiation damage between split doses. Studies show that it is a powerful cytotoxic agent as well and selectively operates against hypoxic cells.
Radiobiological properties of high-energy cyclotron-produced neutrons were investigated. The survival curve for mammalian cells exposed to 35 MeV neutrons has an appreciable shoulder, but exhibits a significant initial slope at low doses. split-dose experiments, using doses comparable to the daily fractions of neutron therapy, indicate no repair of sublethal damage. The nitroimidazoles, and particularly Flagyl, have been shown to selectively sensitize hypoxic cells to the effects of x-rays. Experiments demonstrated that Flagyl is equally effective in reducing the oxygen enhancement ratio for high-energy neutrons. Hypoxic sensitizers must by regarded as an adjunct to neutron therapy, rather than as a competitor.
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