title: Myricetin, quercetin, (+)-catechin and (-)-epicatechin protect against N-nitrosamines-induced DNA damage in human hepatoma cells.
abstract: The aim of this study was to investigate the protective effect of myricetin, quercetin, (+)-catechin and (-)-epicatechin, against N-nitrosodibutylamine (NDBA) and N-nitrosopiperidine (NPIP)-induced DNA damage in human hepatoma cells (HepG2). DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or Comet assay. (+)-Catechin at the lowest concentration (10 microM) showed the maximum reduction of DNA strand breaks (23%), the formation of endonuclease III (Endo III, 19-21%) and formamidopyrimidine-DNA glycosylase (Fpg, 28-40%) sensitive sites induced by NDBA or NPIP. (-)-Epicatechin also decreased DNA strand breaks (10 microM, 20%) and the oxidized pyrimidines/purines (33-39%) induced by NDBA or NPIP, respectively. DNA strand breaks induced by NDBA or NPIP were weakly reduced by myricetin at the lowest concentration (0.1 microM, 10-19%, respectively). Myricetin also reduced the oxidized purines (0.1 microM, 17%) and pyrimidines (0.1 microM, 15%) induced by NDBA, but not the oxidized pyrimidines induced by NPIP. Quercetin did not protect against NDBA-induced DNA damage, but it reduced the formation of Endo III and Fpg sensitive sites induced by NPIP (0.1 microM, 17-20%, respectively). In conclusion, our results indicate that (+)-catechin and (-)-epicatechin at the concentrations tested protect human derived cells against oxidative DNA damage effects of NDBA and NPIP. However, myricetin at the concentrations tested only protects human cells against oxidative DNA damage induced by NDBA and quercetin against oxidative DNA damage induced by NPIP.
authors.affiliation: Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Delgado
authors.forename: A I
authors.initials: AI
authors.lastname: Haza
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: P
authors.initials: P
authors.lastname: Morales
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D020552:Comet Assay; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D009602:Nitrosamines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011794:Quercetin / Q000737:chemistry / Q000145:classification / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D005419:Flavonoids; D009153:Mutagens; D009602:Nitrosamines; C002743:N-nitrosopiperidine; C040015:myricetin; C012279:dibutylnitrosamine; D002392:Catechin; D011794:Quercetin