title: Evaluation of the protective effect of ascorbic acid on nitrite- and nitrosamine-induced cytotoxicity and genotoxicity in human hepatoma line.
abstract: Nitrites are ubiquitous environmental contaminants present in drinking water and foods. Nitrosamines can be formed endogenously from nitrate and nitrite and secondary amines or may be present in food, tobacco smoke, and drinking water. The major goal of this work was to evaluate the cytotoxic, reactive oxygen species (ROS)-producing and genotoxic effects of nitrite and nitrosamines and the possible protection by ascorbic acid in HepG2 cells. It was found that nitrite, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosomorpholine (NMOR) decreased cell viability, increased intracellular ROS production, and caused genotoxicity. Compared to untreated cells as determined by alkaline Comet assay, nitrite, NDMA, NDEA, and NMOR raised the tail intensity up to 1.18-, 3.79-, 4.24-, and 4.16-fold, respectively. Ascorbic acid (AA, 10 microM) increased cell viability and reduced ROS production significantly (p < 0.05). Additionally, AA treatment decreased the tail intensity caused by nitrite, NDMA, NDEA, and NMOR to 33.74%, 58.6%, 44.32%, and 43.97%, respectively. It can be concluded that ascorbic acid was able to reduce both tail intensity and tail moment in all of the nitrosamine treatments, particularly in NDMA. AA protected HepG2 cells against genotoxic effects caused by nitrosamines. This protection might be through different mechanisms, some of which are not still understood in depth. The future interest will be to understand which pathways are influenced by antioxidants, particularly by AA, and the outcomes of this prevention in other cell line types.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey. erkekp@hacettepe.edu.tr
authors.forename: Pinar
authors.initials: P
authors.lastname: Erkekoglu
authors.forename: Terken
authors.initials: T
authors.lastname: Baydar
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects; D004052:Diethylnitrosamine / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009153:Mutagens / Q000633:toxicity*; D009573:Nitrites / Q000633:toxicity*; D009602:Nitrosamines / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D009153:Mutagens; D009573:Nitrites; D009602:Nitrosamines; D017382:Reactive Oxygen Species; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine; D004128:Dimethylnitrosamine; D001205:Ascorbic Acid