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 (Delta Psi 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.
Saquib
Quaiser
Q
DNA Research Chair, Department of Zoology, King Saud University, Riyadh, Saudi Arabia.
Al-Khedhairy
Abdulaziz A
AA
Singh
Braj R
BR
Arif
Jamal M
JM
Musarrat
Javed
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002417:Cattle; D004247:DNA; D053960:DNA Breaks / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016296:Mutagenesis; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013875:Thiophanate / Q000633:toxicity*
D004272:DNA, Mitochondrial; D005659:Fungicides, Industrial; D017382:Reactive Oxygen Species; D013875:Thiophanate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C427203:calf thymus DNA; D003849:Deoxyguanosine