title: 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: Department of Pharmacology and Toxicology, Faculty of Pharmacy, MISR for Science and Technology University, Cairo, Egypt.
authors: Naglaa
authors: N
authors: Assaf
authors: Neveen A
authors: NA
authors: Salem
authors: Wagdy K B
authors: WK
authors: Khalil
authors: Hanaa H
authors: HH
authors: Ahmed
mesh_terms: D000097:Acetonitriles / Q000633:toxicity*; D000410:Alanine Transaminase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000032:analysis / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000097:Acetonitriles; D000975:Antioxidants; D002273:Carcinogens; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C051715:dibromoacetonitrile