Journal
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
Volume 18, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/ijerph18168591
Keywords
gene expression; genotoxicity; pesticides; reactive oxygen species; risk assessment
Funding
- Italian project Studio in vitro sui potenziali effetti tossicologici dei principi attivi e loro miscele utilizzati contro la pernospora e l'oidio nel disciplinare trentino e nel disciplinare tradizionale: strumenti per formazione ed informazione della pop
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Mancozeb and zoxamide showed cytotoxicity in HepG2 and A549 cells at high concentrations, with slightly different mechanisms of action but no increase in intracellular reactive oxygen species. While Mancozeb exhibited genotoxicity, Zoxamide did not induce DNA damage, yet both had aneugenic potential.
Mancozeb (MZ) and zoxamide (ZOX) are fungicides commonly used in pest control programs to protect vineyards. Their toxic and genotoxic potential were investigated in vitro on HepG2 and A549 cell lines at environmentally relevant concentrations. Cytotoxicity, apoptosis, necrosis and intracellular reactive oxygen species (ROS), comet assay and a micronucleus test with CREST immunofluorescence were used. The expression of a panel of genes involved in apoptosis/necrosis (BAX/BCL2), oxidative stress (NRF2), drug metabolism (CYP1A1) and DNA repair (ERCC1/OGG1) was evaluated by real-time PCR. Both fungicides were cytotoxic at the highest tested concentrations (295.7 and 463.4 mu M, respectively); MZ induced necrosis, ZOX did not increase apoptosis but modulated BAX and BCL2 expression, suggesting a different mechanism. Both compounds did not increase ROS, but the induction of CYP1A1 and NRF2 expression supported a pro-oxidant mechanism. The comet assay evidenced MZ genotoxicity, whereas no DNA damage due to ZOX treatment was observed. Positive micronuclei were increased in both cell lines treated with MZ and ZOX, supporting their aneugenic potential. ERCC1 and OGG1 were differently modulated, indicating the efficient activation of the nucleotide excision repair system by both fungicides and the inhibition of the base excision repair system by MZ. Overall, MZ confirmed its toxicity and new ZOX-relevant effects were highlighted.
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