title: A novel genotoxic aspect of thiabendazole as a photomutagen in bacteria and cultured human cells.
abstract: Thiabendazole (TBZ) is a post-harvest fungicide commonly used on imported citrus fruits. We recently found that TBZ showed photomutagenicity with UVA-irradiation in the Ames test using plate incorporation method. In the present study, potential of DNA-damaging activity, mutagenicity, and clastogenicity were investigated by short pulse treatment for 10 min with TBZ (50-400 microg/ml) and UVA-irradiation (320-400 nm, 250 microW/cm2) in bacterial and human cells. UVA-irradiated TBZ caused DNA damage in Escherichia coli and human lymphoblastoid WTK1 cells assayed, respectively, by the umu-test and the single cell gel electrophoresis (comet) assay. In a modified Ames test using Salmonella typhimurium and E. coli, strong induction of -1 frameshift mutations as well as base-substitution mutations were detected. TBZ at 50-100 microg/ml with UVA-irradiation significantly induced micronuclei in WTK1 cells in the in vitro cytochalasin-B micronucleus assay. Pulse treatment for 10 min with TBZ alone did not show any genotoxicity. Although TBZ is a spindle poison that induces aneuploidy, we hypothesize that the photogenotoxicity of TBZ in the present study was produced by a different mechanism, probably by DNA adduct formation. We concluded that UVA-activated TBZ is genotoxic in bacterial and human cells in vitro.
authors.affiliation: Biomedical Research Laboratories, Kureha Chemical Industry Co., 3-26-2 Hyakunin-cho, Shinjuku, Tokyo 169-8503, Japan. akanuma@kureha.co.jp
authors.forename: Mie
authors.initials: M
authors.lastname: Watanabe-Akanuma
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohta
authors.forename: Yu F
authors.initials: YF
authors.lastname: Sasaki
mesh_terms: D001419:Bacteria / Q000187:drug effects*; D002478:Cells, Cultured; D004249:DNA Damage; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013827:Thiabendazole / Q000633:toxicity*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D009153:Mutagens; D013827:Thiabendazole