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Fungicide prochloraz induces oxidative stress and DNA damage in vitro
Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Box 7028, SE-75007 Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Box 7028, SE-75007 Uppsala, Sweden..
2016 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 91, 36-41 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 91, 36-41 p.
Keyword [en]
DNA damage, Nrf2, Oxidative stress, Prochloraz
National Category
Pharmacology and Toxicology Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:uu:diva-297807DOI: 10.1016/j.fct.2016.03.002ISI: 000375629200004PubMedID: 26945613OAI: oai:DiVA.org:uu-297807DiVA: diva2:943500
Funder
Swedish Research Council Formas, 2014-1435
Available from: 2016-06-28 Created: 2016-06-28 Last updated: 2016-06-28Bibliographically approved

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