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

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Genotoxic fungicide methyl thiophanate as an oxidative stressor

inducing 8-oxo-7,8-dihydro- 2' -deoxyguanosine adducts in DNA and

mutagenesis.

Saquib Q, Al-Khedhairy AA, Singh BR, Arif JM, Musarrat J.

J Environ Sci

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

 

DNA Research Chair, Department of Zoology, King Saud University, Riyadh,

Saudi Arabia.

Abstract

Dimethyl 4,4' -(O-phenylene) bis(3-thioalloph anate), 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'-Dichlorodihyd ro

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.

PMID: 20390929 [PubMed - in process]