Split Dose Cytotoxic Experiments with Misonidazole

Overview

Journal Br J Cancer

Specialty Oncology

Date 1978 Jul 1

PMID 687510

Citations 5

Authors

I J Stratford

Affiliations

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Abstract

The toxicity of misonidazole (1-(2-nitroimidazol-1-yl)-3-methoxy-2-propanol) towards mammalian cells in vitro has been determined as a function of O2 tension. Misonidazole under hypoxic conditions (less than 10 Parts/10(6) O2) shows the greatest toxicity. Split-dose experiments indicate that lethal damage can be "repaired" by O2, the magnitude of this repair being time dependent and a function of O2 concentration, with maximum repair in air seen after 2 h at 37 degree C. Unlike radiation damage this repair is not inhibited by modest hyperthermia (41 degrees C) during the split-dose interval. The implication of these results as regards the mechanism of misonidazole toxicity under anaerobic conditions is discussed.

Citing Articles

Sulphydryls, ascorbate and oxygen as modifiers of the toxicity and metabolism of misonidazole in vitro.

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Cytotoxicity of metronidazole (Flagyl) and misonidazole (Ro-07-0582): enhancement by lactate.

Mahood J, Willson R Br J Cancer. 1981; 43(3):350-4.

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Enhancing effect of pre-treatment of cells with misonidazole in hypoxia on their response to melphalan in air.

Smith E, Stratford I, Adams G Br J Cancer. 1982; 46(1):117-26.

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Cell-cycle inhibition by misonidazole of human cells cultivated in vitro under aerobic conditions.

Lindmo T, Pettersen E, Wibe E Br J Cancer. 1979; 40(5):755-60.

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Ascorbate anion potentiates cytotoxicity of nitro-aromatic compounds under hypoxic and anoxic conditions.

Koch C, Howell R, Biaglow J Br J Cancer. 1979; 39(3):321-9.

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