title: Toxicity of diuron in human cancer cells.
abstract: Diuron is a substituted phenylurea used as a herbicide to control broadleaf and grass weeds and as a biocidal antifouling agent. Diuron is carcinogenic in rat urinary bladder and toxic to the reproductive system of oysters, sea urchins and lizards. The few studies carried out in human cells do not include the genotoxicity of diuron. We have investigated the toxicity of diuron in human breast adenocarcinoma (MCF-7) and human placental choriocarcinoma (BeWo) cells. The production of reactive oxygen species (ROS) was statistically significantly increased in both cell lines but only at the highest 200 μM concentration. Diuron clearly reduced the viability of BeWo, but not MCF-7 cells. The relative cell number was decreased in both cell lines indicative of inhibition of cell proliferation. In the Comet assay, diuron increased DNA fragmentation in MCF-7 but not in BeWo cells. The expressions of p53 protein, a marker for cell stress, and p21 protein, a transcriptional target of p53, were increased, but only in MCF-7 cells. In conclusion, our results suggest that diuron is cytotoxic and potentially genotoxic in a tissue-specific manner and that ROS play a role in its toxicity. Thus, exposure to diuron may exert harmful effects on fetal development and damage human health.
authors.affiliation: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy/Toxicology, Yliopistonranta 1 C, 70210 Kuopio, Finland. Electronic address: Marjo.Huovinen@uef.fi.
authors.forename: Marjo
authors.initials: M
authors.lastname: Huovinen
authors.affiliation: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy/Toxicology, Yliopistonranta 1 C, 70210 Kuopio, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Loikkanen
authors.affiliation: University of Eastern Finland, Department of Environmental Science, Kuopio, Finland.
authors.forename: Jonne
authors.initials: J
authors.lastname: Naarala
authors.affiliation: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy/Toxicology, Yliopistonranta 1 C, 70210 Kuopio, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vähäkangas
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004237:Diuron / Q000633:toxicity*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D061986:MCF-7 Cells; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D006540:Herbicides; D009153:Mutagens; D017382:Reactive Oxygen Species; D004237:Diuron; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: BeWo cells; Genotoxicity; Herbicides; MCF-7 cells; Mechanism of toxicity