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Toxicity of diuron in human cancer cells
Marjo Huovinen1, Jarkko Loikkanen1, Jonne Naarala2
1University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy/Toxicology, Yliopistonranta 1 C, 70210 Kuopio, Finland.
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.
Insights
Diuron herbicide is toxic to human cells, causing DNA damage and reduced cell growth. Its harmful effects may impact fetal development and overall human health, highlighting the need for caution.
Area of Science:
- Environmental toxicology
- Cell biology
- Genotoxicity
Background:
- Diuron is a widely used herbicide and antifouling agent.
- Known to be carcinogenic in rats and toxic to various aquatic and terrestrial species.
- Limited data exists on diuron's genotoxicity in human cells.
Purpose of the Study:
- To investigate the toxicity and genotoxicity of diuron in human breast (MCF-7) and placental (BeWo) cell lines.
- To assess the role of reactive oxygen species (ROS) in diuron-induced toxicity.
Main Methods:
- Exposure of MCF-7 and BeWo cells to varying concentrations of diuron.
- Measurement of reactive oxygen species (ROS) production.
- Cell viability and proliferation assays (relative cell number).
- Comet assay for DNA fragmentation.
- Western blot analysis for p53 and p21 protein expression.
Main Results:
- Increased ROS production in both cell lines at high diuron concentrations (200 μM).
- Diuron reduced viability in BeWo cells but not MCF-7 cells.
- Inhibited cell proliferation in both cell lines.
- Increased DNA fragmentation in MCF-7 cells, but not BeWo cells.
- Upregulated p53 and p21 protein expression in MCF-7 cells.
Conclusions:
- Diuron exhibits tissue-specific cytotoxicity and potential genotoxicity in human cells.
- ROS plays a role in diuron's toxic mechanisms.
- Potential risks to fetal development and human health warrant further investigation.
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