Toxicity of nitrobenzene compounds towards isolated hepatocytes: dependence on reduction potential
- 1 January 1990
- journal article
- research article
- Published by Taylor & Francis in Xenobiotica
- Vol. 20 (9) , 945-955
- https://doi.org/10.3109/00498259009046910
Abstract
1. The cytotoxicity of p-substituted nitrobenzenes towards isolated hepatocytes under aerobic or hypoxic conditions has been determined. The nitrobenzene concentrations required to cause 50% cytotoxicity in 2h was a function of the one-electron reduction potential of the nitrobenzene, with the more cytotoxic compounds having the strongest electron-withdrawing substituents. 2. The effectiveness of the nitrobenzenes at causing cytotoxicity under aerobic but not hypoxic conditions was markedly increased if hepatocyte catalase was inhibited with azide. 3. Nitrobenzenes at cytotoxic concentrations induced cyanide-resistant respiration in isolated hepatocytes. Their effectiveness correlated with their cytotoxicity. 4. The rate of oxygen activation of these nitrobenzens by ascorbate was also a function of the one-electron reduction potential. The nitro compounds with the strongest electron-withdrawing substiuents were the most rapidly reduced. 5. Most nitrobenznes were more cytotoxic under aerobic than hypoxic conditions. Ascorbate enhanced hypoxic, but not aerobic, cytotoxicity. 6. It was concluded that the cytotoxicity of different nitrobenzenes is related to their ease of reduction to nitro radical anions and nitrosobenzenes. Aerobic cytotoxicity is probably initiated by redox cycling and oxygen activation by the nitro radical anions whereas hypoxic cytotoxicity is probably initiated by the alkylation of macromolecules by nitrosobenzene metabolites.This publication has 24 references indexed in Scilit:
- Nitrosoimidazoles: highly bactericidal analogs of 5-nitroimidazole drugsJournal of Medicinal Chemistry, 1988
- Metabolism of Nitroaromatic CompoundsDrug Metabolism Reviews, 1987
- Hypoxia-mediated druGS FOR RADIATION AND CHEMOTHERAPYCancer, 1981
- The activity of nitro-compounds against Bacteroides fragilis is related to their electron affinityJournal of Antimicrobial Chemotherapy, 1981
- THE OXIDATION OF ASCORBATE BY ELECTRON AFFINIC DRUGS AND CARCINOGENSPhotochemistry and Photobiology, 1978
- Activity-electroreduction relationship of antimicrobial metronidazole analogsJournal of Medicinal Chemistry, 1978
- Ascorbate-enhanced Cytotoxicity of misonidazoleNature, 1978
- Cytotoxicity and DNA damage to mammalian cells by nitrofuransChemico-Biological Interactions, 1977
- Mammalian cell toxicity of nitro compounds: Dependence upon reduction potentiaklBiochemical and Biophysical Research Communications, 1976
- DISTRIBUTION OF ASCORBIC ACID, METABOLITES AND ANALOGUES IN MAN AND ANIMALSAnnals of the New York Academy of Sciences, 1975