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

• Published in: Journal of environmental science and health. Part B, Pesticides, food contaminants, and agricultural wastes Vol. 45; no. 1; pp. 40 - 45
• Main Authors: Saquib, Quaiser, Al-Khedhairy, Abdulaziz A, Singh, Braj R, Arif, Jamal M, Musarrat, Javed
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Taylor & Francis Group 01.01.2010; Taylor & Francis; Taylor & Francis Ltd
• Subjects: 8-oxodG; Agronomy. Soil science and plant productions; Animals; Biological and medical sciences; Carcinogens; Cattle; Deoxyguanosine - analogs & derivatives; DNA; DNA adducts; DNA Breaks - drug effects; DNA damage; DNA Damage - drug effects; DNA, Mitochondrial - drug effects; Dose-Response Relationship, Drug; dyes; Fundamental and applied biological sciences. Psychology; Fungicide; fungicides; Fungicides, Industrial - toxicity; Genetics and breeding of economic plants; genotoxicity; human cell lines; Humans; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - metabolism; membrane potential; methyl thiophanate; mitochondria; mitochondrial membrane potential; Mutagenesis; mutagenicity; Oxidation; Oxidation-Reduction; oxidative stress; Oxidative Stress - drug effects; Pesticides; Plant breeding: fundamental aspects and methodology; reactive oxygen species; Reactive Oxygen Species - metabolism; rhodamine; ROS; Soil and water pollution; Soil science; Studies; Thiophanate - toxicity; thiophanate-methyl; thymus gland; toxicity testing; Oxidative stress; mutagenicity; Toxicity; methyl thiophanate; Pesticides; Genotoxicity; mitochondrial membrane potential; Systemic; Mutagen; Fungicide; 8-oxodG; Mitochondria; Mutagenesis; DNA; ROS; Environment; Membrane potential; Carbamate; Adduct
• ISSN: 0360-1234; 1532-4109
• DOI: 10.1080/03601230903404325

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 32 P-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.