title: Fungicide prochloraz induces oxidative stress and DNA damage in vitro.
abstract: Prochloraz is widely used in horticulture and agriculture, e.g. as a post-harvest anti-mold treatment. Prochloraz is a known endocrine disruptor causing developmental toxicity with multiple mechanisms of action. However, data are scarce concerning other toxic effects. Since oxidative stress response, with formation of reactive oxygen species (ROS), is a common mechanism for different toxic endpoints, e.g. genotoxicity, carcinogenicity and teratogenicity, the aim of this study was to investigate if prochloraz can induce oxidative stress and/or DNA damage in human cells. A cell culture based in vitro model was used to study oxidative stress response by prochloraz, as measured by the activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), a key molecule in oxidative defense mechanisms. It was observed that prochloraz induced oxidative stress in cultured human adrenocortical H295R and hepatoma HepG2 cells at non-toxic concentrations. Further, we used Comet assay to investigate the DNA damaging potential of prochloraz, and found that non-toxic concentrations of prochloraz induced DNA damage in HepG2 cells. These are novel findings, contradicting previous studies in the field of prochloraz and genotoxicity. This study reports a new mechanism by which prochloraz may exert toxicity. Our findings suggest that prochloraz might have genotoxic properties.
authors.affiliation: Swedish University of Agricultural Sciences, Department of Biomedical Sciences and Veterinary Public Health, Box 7028, SE-750 07 Uppsala, Sweden. Electronic address: johan.lundqvist@slu.se.
authors.forename: J
authors.initials: J
authors.lastname: Lundqvist
authors.affiliation: Uppsala University, Department of Pharmaceutical Biosciences, Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Hellman
authors.affiliation: Swedish University of Agricultural Sciences, Department of Biomedical Sciences and Veterinary Public Health, Box 7028, SE-750 07 Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Oskarsson
mesh_terms: D004249:DNA Damage / Q000187:drug effects*; D005659:Fungicides, Industrial / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D005659:Fungicides, Industrial; D007093:Imidazoles; C045362:prochloraz
keywords: DNA damage; Nrf2; Oxidative stress; Prochloraz