title: Diphenyl diselenide protects cultured MCF-7 cells against tamoxifen-induced oxidative DNA damage.
abstract: Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organoselenium compounds. Studies have shown its interesting pharmacodinamic properties, as antioxidant, antimutagenic and antitumoral effects. Here we report the antigenotoxic properties of DPDS against tamoxifen (TAM)-induced oxidative DNA damage in MCF-7 cultured cell line. We determined the cytotoxicity by lactate dehydrogenase (LDH) leakage assay and evaluated oxidative DNA damage by modified comet assay employing the enzymes formamidopyrimidine DNA-glycosylase (Fpg) and endonuclease III (Endo III). Our results demonstrate that the cellular effects of DPDS appear to be complex and concentration-dependent. The present findings show that DPDS is not genotoxic (at concentrations lower than 2.0μmol/L) in MCF-7 cells, as observed in the modified comet assay. Moreover, DPDS protects against TAM-induced oxidative DNA damage, probably by its antioxidant activity, without interfering with its cytotoxicity. In this manner, the treatment with low concentrations of DPDS, a synthetic organoselenium compound, could be used as a potent antigenotoxic agent to prevent the risk of cancer induction triggered by tamoxifen hormone therapy. Thereby, more studies concerning the toxicity of DPDS and its structural derivatives are still necessary for future safe therapeutic application and development of novel chemopreventive compounds for combined therapy in breast cancer.
authors.affiliation: Programa de Pós-Graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil (ULBRA), Canoas-RS, Brazil.
authors.forename: M T
authors.initials: MT
authors.lastname: Melo
authors.forename: I M
authors.initials: IM
authors.lastname: de Oliveira
authors.forename: I
authors.initials: I
authors.lastname: Grivicich
authors.forename: T N
authors.initials: TN
authors.lastname: Guecheva
authors.forename: J
authors.initials: J
authors.lastname: Saffi
authors.forename: J A P
authors.initials: JA
authors.lastname: Henriques
authors.forename: R M
authors.initials: RM
authors.lastname: Rosa
mesh_terms: D016587:Antimutagenic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000473:pathology; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D013629:Tamoxifen / Q000633:toxicity*
chemical_list: D016587:Antimutagenic Agents; D018931:Antineoplastic Agents, Hormonal; D000975:Antioxidants; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D013629:Tamoxifen; C061132:diphenyldiselenide