Oncogenic transformations in vitro produced by misonidazole.

The C3H/10T 1/2 cell line, cultured in vitro, was used to study the induction of oncogenic transformations produced by electron affinic compounds which function as hypoxic cell radiosensitizers. The relationship between the incidence of oncogenic transformations and drug concentration was obtained for 3-day exposures to misonidazole. At a concentration of 1 mM, a comparison was made of the carcinogenic potential of misonidazole, desmethylmisonidazole, Ro-07-0741, and SR 2508. Misonidazole and desmethylmisonidazole induced similar frequencies of transformation, while the frequency was doubled for Ro-07-0741 and increased by a factor of 5 for SR 2508. The relative carcinogenicity of the various alternatives to misonidazole is clearly a factor in choosing the next compound to be tested in the clinic.