title: Evaluation of DNA Damage in HepG2 Cells and Mutagenicity of Garcinielliptone FC, A Bioactive Benzophenone.
abstract: Garcinielliptone FC (GFC) is a polyprenylated benzophenone isolated from the hexanic extract of Platonia insignis seeds with potential pharmacological effects on the central nervous system. In a pre-clinical study, this compound showed anticonvulsant action, becoming a candidate to treat epilepsy disorders. However, genotoxicological aspects of GFC should be known to ensure its safe use. This study investigated the cytotoxic, genotoxic, and mutagenic effects of GFC. Cytotoxicity was evaluated using the colorimetric assay of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) in human hepatoma cells (HepG2) (2-100 μg/mL) for 3, 6 and 24 hr. The genotoxic and mutagenic potentials were analysed using the alkaline version of the comet assay, the cytokinesis-block micronucleus cytome assay in HepG2 cells, and the Salmonella/microsome assay with the strains TA98, TA97a, TA100, TA102 and TA1535, with and without metabolic activation. GFC concentrations above 50 μg/mL were cytotoxic at all experimental times. Viability of HepG2 cells was higher than 70% after exposure to GFC 2-30 μg/mL for 3 hr in the MTT test. No GFC concentration was mutagenic or genotoxic in the Salmonella/microsome and comet assays. Nuclear division index decreased, indicating the cytotoxic effect of the compound, while micronucleus and nuclear bud frequencies rose after treatment with the highest GFC concentration tested (30 μg/mL). Nucleoplasmatic bridges were not observed. The results indicate that GFC is cytotoxic and mutagenic to mammalian cells, pointing to the need for further studies to clarify the toxicological potentials of this benzophenone before proceeding to clinical studies.
authors.affiliation: Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Lismare
authors.initials: L
authors.lastname: da Silva Prado
authors.affiliation: Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: da Silva
authors.affiliation: Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Ana Letícia Hilario
authors.initials: ALH
authors.lastname: Garcia
authors.affiliation: Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Fernanda Brião Menezes
authors.initials: FBM
authors.lastname: Boaretto
authors.affiliation: Laboratory of Cancer Biology, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Ivana
authors.initials: I
authors.lastname: Grivicich
authors.affiliation: Laboratory of Cancer Biology, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Lucas Umpierre
authors.initials: LU
authors.lastname: Conter
authors.affiliation: Graduate Program in Pharmacy, Health Sciences Center, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
authors.forename: Aguisson
authors.initials: A
authors.lastname: de Oliveira Salvi
authors.affiliation: Graduate Program in Pharmacy, Health Sciences Center, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
authors.forename: Flávio Henrique
authors.initials: FH
authors.lastname: Reginatto
authors.affiliation: Laboratory of Pharmacognosy and Phytochemistry, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Suele Bierhals
authors.initials: SB
authors.lastname: Vencato
authors.affiliation: Laboratory of Pharmacognosy and Phytochemistry, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Barros Falcão Ferraz
authors.affiliation: Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA), Canoas, Brazil.
authors.forename: Jaqueline Nascimento
authors.initials: JN
authors.lastname: Picada
mesh_terms: D004249:DNA Damage; D056945:Hep G2 Cells; D006801:Humans; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects; D014315:Triterpenes / Q000633:toxicity*
chemical_list: D014315:Triterpenes; C573355:garcinielliptone FC