In vitro metabolism of misonidazole.
Misonidazole (MISO) is a nitroimidazole drug currently undergoing clinical trials as a radiosensitizer of hypoxic tumour cells. The drug is also toxic to such cells, probably because of metabolic activation of the nitro group under hypoxia. The metabolic fate of 14C-labelled MISO is examined, using hypoxic mammalian (CHO) cells in vitro. Organic-soluble and acid-soluble metabolites are formed, and radioactivity is bound to macromolecules. The organic-soluble products are separated by TLC and HPLC. Evidence is presented to show that one of the metabolites is hydroxylamino-misonidazole. The significance of metabolic nitroreduction is discussed.
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D006898:Hydroxylamines / Q000378:metabolism; D008920:Misonidazole / Q000378:metabolism*; D009593:Nitroimidazoles / Q000378:metabolism*; D010100:Oxygen; D013997:Time Factors
D006898:Hydroxylamines; D009593:Nitroimidazoles; D008920:Misonidazole; D010100:Oxygen