Toxicological Comparison of Mancozeb and Zoxamide Fungicides at Environmentally Relevant Concentrations by an In Vitro Approach.
Gabriele LoriTassinari RobertaLaura NarcisoIon UdroiuAntonella SguraFrancesca MaranghiSabrina TaitPublished in: International journal of environmental research and public health (2021)
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 µM, 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.
Keyphrases
- dna repair
- dna damage
- oxidative stress
- diabetic rats
- induced apoptosis
- reactive oxygen species
- poor prognosis
- ischemia reperfusion injury
- dna damage response
- endoplasmic reticulum stress
- real time pcr
- cell death
- binding protein
- high throughput
- public health
- cell cycle arrest
- high resolution
- drug induced
- human health
- mass spectrometry
- risk assessment
- climate change
- signaling pathway
- stress induced
- electronic health record
- replacement therapy