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

• Published in: Food and chemical toxicology 2011-12, Vol.49 (12), p.3055-3062
• Main Authors: Assaf, Naglaa, Salem, Neveen A., Khalil, Wagdy K.B., Ahmed, Hanaa H.
• Format: Article
• Language: English
• Subjects: Acetonitriles - toxicity; Alanine transaminase; Alanine Transaminase - analysis; Alanine Transaminase - metabolism; Animals; antioxidant activity; antioxidants; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; Aspartate Aminotransferases - analysis; Aspartate Aminotransferases - metabolism; aspartate transaminase; Biological and medical sciences; Carcinogens - toxicity; Dibromoacetonitrile; disinfectants; DNA damage; DNA Damage - drug effects; DNA fragmentation; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; erythrocytes; Erythrocytes - drug effects; Erythrocytes - metabolism; hepatocyte growth factor; hepatocytes; Hepatotoxicity; liver; Liver - drug effects; Liver - pathology; Male; malondialdehyde; Malondialdehyde - analysis; Medical sciences; oral administration; oxidants; Oxidative stress; Oxidative Stress - drug effects; proto-oncogenes; Rats; Rats, Sprague-Dawley; tissues; Toxicology; Tumor initiating genes
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2011.09.030

► In this study we investigated the hepatotoxic effect of dibromoacetonitrile. ► Dibromoacetonitrile induces DNA damage and alteration in the expression of tumor initiating genes. ► This effect is mediated through increased oxidative stress and disturbance in the oxidant/antioxidant status in liver. 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 (60mg/kg) and fractionated (7.5mg/kg) doses, weekly twice for 4weeks and once weekly for 8weeks. 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 4weeks. 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.