Genotoxicity of ferric oxide nanoparticles in Raphanus sativus: Deciphering the role of signaling factors, oxidative stress and cell death

We have studied the genotoxic and apoptotic potential of ferric oxide nanoparticles(Fe_2O_3-NPs) in Raphanus sativus(radish).Fe_2O_3-NPs retarded the root length and seed germination in radish.Ultrathin sections of treated roots showed subcellular localization of Fe_2O_3-NPs,along with the appearance of damaged mitochondria and excessive vacuolization.Flow cytometric analysis of Fe_2O_3-NPs(1.0 mg/m L) treated groups exhibited 219.5%,161%,120.4% and 161.4% increase in intracellular reactive oxygen species(ROS),mitochondrial membrane potential(ΔΨm),nitric oxide(NO) and Ca2+influx in radish protoplasts.A concentration dependent increase in the antioxidative enzymes glutathione(GSH),catalase(CAT),superoxide dismutase(SOD) and lipid peroxidation(LPO) has been recorded.Comet assay showed a concentration dependent increase in deoxyribonucleic acid(DNA) strand breaks in Fe_2O_3-NPs treated groups.Cell cycle analysis revealed 88.4% of cells in sub-G1 apoptotic phase,suggesting cell death in Fe_2O_3-NPs(2.0 mg/m L) treated group.Taking together,the genotoxicity induced by Fe_2O_3-NPs highlights the importance of environmental risk associated with improper disposal of nanoparticles(NPs) and radish can serve as a good indicator for measuring the phytotoxicity of NPs grown in NP-polluted environment.     

Genotoxic fungicide methyl thiophanate as an oxidative stressor inducing 8-oxo-7,8-dihydro-2′ -deoxyguanosine adducts in DNA and mutagenesis

Dimethyl 4,4′ -(O-phenylene)bis(3-thioallophanate), commonly known as methyl thiophanate (MT), is a systemic fungicide and suspected carcinogen to humans. In this study, the oxidative potential of this category-III acute toxicant has been ascertained based on its capacity of inducing reactive oxygen species (ROS) and promutagenic 8-oxo-7,8-dihydro-2′ -deoxyguanosine (8-oxodG) adducts in DNA. The discernible MT dose-dependent reduction in fluorescence intensity of a cationic dye rhodamine (Rh-123) in human lymphocytes and increased fluorescence intensity of 2′,7′-Dichlorodihydro fluorescein diacetate (DCFH-DA) treated cells signifies decreased mitochondrial membrane potential (Δ Ψ m) due to intracellular ROS generation. The ³²P-post-labeling assay demonstrated the MT-induced 8-oxodG adduct formation in calf thymus DNA. Thus, it is concluded that MT, as a potent oxidative stressor, produces ROS leading to mitochondrial dysfunction, oxidative DNA damage and mutagenesis.