title: Evaluation of the genotoxic and anti-genotoxic activities of silybin in human hepatoma cells (HepG2).
abstract: Silybin (SB), a constituent of the medicinal plant Silybum marianum, is reported to be a potent hepatoprotective agent, but little is currently known regarding its genotoxicity, mutagenicity and potential chemopreventive properties. In this study, we evaluated the ability of SB to induce DNA migration and micronuclei (MN) formation in human hepatoma cells (HepG2). Also, possible preventive effects of SB on MN formation induced by three different mutagens, bleomycin (BLEO), benzo[a]pyrene (B[a]P) and aflatoxin B(1) (AFB(1)), were studied. To clarify the possible mechanism of SB antimutagenicity, three treatment protocols were applied: pretreatment, in which SB was added before the application of the mutagens; simultaneous treatment, in which SB was added during treatment and post-treatment, in which SB was added after the application of the mutagens. At concentrations up to 100 microM, SB was non-genotoxic, while at a concentration of 200 microM, SB induced DNA migration, generated oxidized DNA bases, reduced cell viability, decreased the replicative index of the cells and induced oxidative stress. It is noteworthy that SB was able to reduce the genotoxic effect induced by B[a]P, BLEO and AFB(1) in pretreatment and simultaneous treatments but had no significant effect on DNA damage induction in post-treatment. Taken together, our findings indicate that SB presents anti-genotoxic activity in vitro, which suggests potential use as a chemopreventive agent.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Professor Lineu Prestes 748, CEP 05508-900, São Paulo, Brasil. jpangeli@iq.usp.br
authors.forename: José Pedro Friedmann
authors.initials: JP
authors.lastname: Angeli
authors.forename: Gustavo Rafael Mazzaron
authors.initials: GR
authors.lastname: Barcelos
authors.forename: Juliana Mara
authors.initials: JM
authors.lastname: Serpeloni
authors.forename: Fernando
authors.initials: F
authors.lastname: Barbosa
authors.forename: Armen
authors.initials: A
authors.lastname: Nersesyan
authors.forename: Mario Sergio
authors.initials: MS
authors.lastname: Mantovani
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity; D001564:Benzo(a)pyrene / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000633:toxicity*
chemical_list: D029968:Escherichia coli Proteins; D009153:Mutagens; D017382:Reactive Oxygen Species; D012838:Silymarin; D001761:Bleomycin; D001564:Benzo(a)pyrene; D000077385:Silybin; D004247:DNA; D016604:Aflatoxin B1; D004720:Endonucleases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli