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

J Environ Sci Health B. 2010 Jan;45(1):40-5. 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 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Cattle
  • DNA
  • DNA Breaks / drug effects*
  • DNA Damage / drug effects*
  • DNA, Mitochondrial / drug effects
  • Deoxyguanosine / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Fungicides, Industrial / toxicity*
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Mutagenesis
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism*
  • Thiophanate / toxicity*


  • DNA, Mitochondrial
  • Fungicides, Industrial
  • Reactive Oxygen Species
  • Thiophanate
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • calf thymus DNA
  • Deoxyguanosine