| Assessment of methyl thiophanate-Cu (II) induced DNA damage in human lymphocytes. | |
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MedLine Citation:
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PMID: 19427896 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dimethyl 4,4'-(O-phenylene)bis(3-thioallophanate), commonly known as methyl thiophanate (MT), is a category-III acute toxicant and suspected carcinogen to humans. Hence, the ability of this benzimidazole class of fungicide to engender DNA strand breaks was investigated using alkaline single cell gel electrophoresis (SCGE), alkaline unwinding and cytokinesis-blocked micronucleus (CBMN) assays. The SCGE of human lymphocytes treated with 1mM MT for 3h at 37 degrees C showed much higher Olive tail moment (OTM) value of 40.3+/-2.6 (p<0.001) vis-à-vis 3.3+/-0.09 in DMSO control. Treatment of cultured lymphocytes for 24h resulted in significantly increased number of binucleated micronucleated (BNMN) cells with a dose dependent reduction in the nuclear division index (NDI). Stoichiometric data revealed the intrinsic property of MT to bind with Cu (II) and its reduction to Cu (I), which is known to form reactive oxygen species (ROS). We have detected the intracellular ROS generation in MT treated lymphocytes and observed an elevated level of MT-induced strand breaks per unit of calf thymus DNA in presence of Cu (II). Overall the data suggested that the formation of MT-Cu (II)-DNA ternary complex and consequent ROS generation, owing to Cu (II)/Cu (I) redox cycling in DNA proximity, is responsible for MT-induced DNA damage. |
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Authors:
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Quaiser Saquib; Abdulaziz A Al-Khedhairy; Saud Al-Arifi; Alok Dhawan; Javed Musarrat |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-08 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 23 ISSN: 1879-3177 ISO Abbreviation: Toxicol In Vitro Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-06 Completed Date: 2009-10-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 848-54 Citation Subset: IM |
Affiliation:
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Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Cattle Cells, Cultured Comet Assay Copper / chemistry* Cytokinesis DNA / drug effects, metabolism DNA Breaks / drug effects* Dose-Response Relationship, Drug Fungicides, Industrial / administration & dosage, chemistry, toxicity Humans Lymphocytes / drug effects, metabolism Male Micronucleus Tests / methods Reactive Oxygen Species / metabolism* Thiophanate / administration & dosage, chemistry, toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Fungicides, Industrial; 0/Reactive Oxygen Species; 23564-05-8/Thiophanate; 7440-50-8/Copper; 9007-49-2/DNA; 91080-16-9/calf thymus DNA |
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