Hypoxic radiosensitizers: prospects for effective compounds with fewer toxic side-effects.

Several radiosensitizing chemicals, including a family of simple nitroimidazoles, were examined in E. coli and compared with misonidazole for toxic side-effects on endpoints such as mutagenesis, cell killing and inhibition of the synthesis of the inducible enzyme beta-galactosidase. While all the compounds were similar to misonidazole or better in radiosensitization, marked differences in the various side effects were found. There results show that for E. coli it is possible to find compounds that sensitize as well as misonidazole but which have decreased mutagenicity and fewer other side-effects. Of the compounds examined, KA121 (2,5-dinitroimidazole) is the most promising for future study because it combines good radiosensitization with low mutagenicity and toxicity.