Evaluation of the potential toxicity of dibromoacetonitrile-induced apoptosis and tumor-initiating activity in rat liver.

Abstract

Dibromoacetonitrile (DBAN) is water disinfectant by-product. Its broad-spectrum toxicity in different test systems in vivo and in vitro has been reported. However, there is a scanty of information regarding dibromoacetonitrile hepatotoxicity. Therefore, this study aimed to investigate the possible mechanisms for dibromoacetonitrile-induced tumor initiation in rat liver cells. Dibromoacetonitrile was orally administered to rats as an acute (60 mg/kg) and fractionated (7.5mg/kg) doses, weekly twice for 4 weeks and once weekly for 8 weeks. Significant increase in malondialdehyde level (approximately 7-, 6- and 4-folds) and extensive depletion in total antioxidant capacity were detected following acute and fractionated doses respectively. Alanine aminotransferase (about 2- and 1-folds) and aspartate aminotransferase (3- and 2-folds) were significantly increased after acute dose and fractionated doses for 4 weeks. Also, these doses of dibromoacetonitrile produced high levels of DNA fragmentation, micronucleated polychromatic erythrocytes and changes in the expression of hepatocyte growth factor gene and proto-oncogenes (c-met and c-myc) in liver tissues. Ability of dibromoacetonitrile to induce DNA damage and alterations in the expression of tumor-initiating genes was suggested to be due to hepatotoxicity, oxidative stress and disturbance in the oxidant/antioxidant status of rat liver.

• Authors: Naglaa Assaf, Neveen A Salem, Wagdy K B Khalil, Hanaa H Ahmed
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 49 Issue 12 Pg. 3055-62 (Dec 2011) ISSN: 1873-6351 [Electronic] England
• PMID: 21986297 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Acetonitriles
• Antioxidants
• Carcinogens
• Malondialdehyde
• Aspartate Aminotransferases
• Alanine Transaminase
• dibromoacetonitrile

Topics

• Acetonitriles (toxicity)
• Alanine Transaminase (analysis, metabolism)
• Animals
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Aspartate Aminotransferases (analysis, metabolism)
• Carcinogens (toxicity)
• DNA Damage (drug effects)
• DNA Fragmentation (drug effects)
• Dose-Response Relationship, Drug
• Erythrocytes (drug effects, metabolism)
• Liver (drug effects, pathology)
• Male
• Malondialdehyde (analysis)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley