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. 1981 Apr;43(4):443-50.
doi: 10.1038/bjc.1981.65.

In vitro metabolism of misonidazole

P D Josephy, B Palcic, L D Skarsgard
Free PMC article

In vitro metabolism of misonidazole

P D Josephy et al. Br J Cancer. 1981 Apr.
Free PMC article

Abstract

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.

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