title: Evaluation of micronuclei in mice bone marrow and antioxidant systems in erythrocytes exposed to α-amanitin.
abstract: α-Amanitin, the main toxic substance from mushroom species (Amanita genus), blocks the activity of RNA polymerase II (Pol II) in mammalian cells causing inhibition of transcription and subsequent synthesis of structural and enzymatic proteins. It has been postulated that α-amanitin generates the increase of reactive oxygen species (ROS) concentration. The micronucleus (MN) test was used on an animal experimental model to evaluate possible potential genotoxic effect of α-amanitin on mice bone marrow cells. At the same time the activity of antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT) as well as concentration of thiobarbituric acid reactive substance (TBARS) were investigated in the lysate of mice erythrocytes. α-Amanitin was administered intraperitoneally at the doses: 0.1, 0.15, and 0.25 mg/kg bw (LD(50) for mice) 48 h prior to sacrification. A statistically significant increase of SOD activity was observed in the hemolysate for all the investigated α-amanitin doses as compared to the negative control (p < 0.05). CAT activity for α-amanitin doses 0.1 and 0.15 mg/kg was higher in comparison to the negative control but the differences were not statistically significant (p > 0.05). However, for the dose 0.25 mg/kg the activity of CAT was statistically significantly higher (p < 0.001). All the tested α-amanitin doses decreased TBARS concentration in the hemolysate as compared to the negative control but the differences were not statistically significant (p > 0.05). A statistically significant increase of mean values of MN percent was found in polychromatic erythrocytes (PCEs) as compared to the negative control for α-amanitin dose 0.1 and 0.25 mg/kg (p < 0.05). For the dose 0.15 mg/kg the mean value of MN percent was higher but it did not demonstrate statistical significance (p > 0.1). The observed disturbances in the activity of the examined antioxidant enzymes in cells exposed in vivo to α-amanitin suggest indirect genotoxic effect of α-amanitin through ROS generation.
authors.affiliation: Department of Biology and Medical Genetics, Medical University of Lodz, Pl. Hallera 1, 90-647 Lodz, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Marciniak
authors.forename: D
authors.initials: D
authors.lastname: Lopaczyńska
authors.forename: E
authors.initials: E
authors.lastname: Kowalczyk
authors.forename: J
authors.initials: J
authors.lastname: Skośkiewicz
authors.forename: M
authors.initials: M
authors.lastname: Witczak
authors.forename: M
authors.initials: M
authors.lastname: Majczyk
authors.forename: W
authors.initials: W
authors.lastname: Grabowicz
authors.forename: T
authors.initials: T
authors.lastname: Ferenc
mesh_terms: D053959:Alpha-Amanitin / Q000633:toxicity*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D011042:Poisons / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D053959:Alpha-Amanitin; D009153:Mutagens; D011042:Poisons; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D004247:DNA; D010088:Oxidoreductases