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Literature DB >> 687510

Split dose cytotoxic experiments with misonidazole.

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.

Entities: Chemical

Mesh：

Substances：

Year: 1978 PMID： 687510 PMCID： PMC2009678 DOI： 10.1038/bjc.1978.172

Source DB: PubMed Journal: Br J Cancer ISSN： 0007-0920 Impact factor: 7.640

18 in total

1. The mechanism of microsomal and mitochondrial nitroreductase. Electron spin resonance evidence for nitroaromatic free radical intermediates.

Authors: R P Mason; J L Holtzman
Journal: Biochemistry Date: 1975-04-22 Impact factor: 3.162

Split dose cytotoxic experiments with misonidazole.

1. The mechanism of microsomal and mitochondrial nitroreductase. Electron spin resonance evidence for nitroaromatic free radical intermediates.

2. Cytotoxicity of two nitroimidazole radiosensitizers in an in vitro tumor model.

3. Ro-07-0582 as a radiosensitizer and cytotoxic agent.

4. Oxygen inhibition of nitroreductase: electron transfer from nitro radical-anions to oxygen.

5. Radiosensitization of hypoxic cells by a nitrofuran; dose-modifying and shoulder effects.

6. Selective chemotherapy of noncycling cells in an in vitro tumor model.

7. Cytotoxicity of Ro-07-0582; enhancement by hyperthermia and protection by cysteamine.

8. Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses.

9. Some factors affecting the specific toxicity of misonidazole towards hypoxic mammalian cells.

10. Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells.

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

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

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

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

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