DNA损伤
分子生物学
活性氧
化学
微核
DNA
微核试验
凝胶电泳
生物化学
生物
毒性
有机化学
作者
Quaiser Saquib,Abdulaziz A. Al-Khedhairy,Saud Alarifi,Alok Dhawan,Javed Musarrat
标识
DOI:10.1016/j.tiv.2009.04.017
摘要
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 1 mM MT for 3 h at 37 °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 24 h 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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