Carbamate insecticide methomyl confers cytotoxicity through DNA damage induction

• Published in: Food and chemical toxicology 2013-03, Vol.53, p.352-358
• Main Authors: Guanggang, Xiang, Diqiu, Li, Jianzhong, Yuan, Jingmin, Guan, Huifeng, Zhai, Mingan, Shi, Liming, Tao
• Format: Article
• Language: English
• Subjects: Alkaline comet assay; Animals; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Carbamates - toxicity; Cell Line; Cell Survival; Comet Assay; DNA Breaks, Single-Stranded; DNA damage; DNA Damage - drug effects; DNA Fragmentation; Drosophila; HEK293 Cells; HeLa Cells; Histones - genetics; Histones - metabolism; Humans; Insecticides - toxicity; Medical sciences; Methomyl; Methomyl - toxicity; Pesticides, fertilizers and other agrochemicals toxicology; Toxicology; γH2AX foci
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2012.12.020

[Display omitted] ► Cytotoxicity of methomyl was investigated. ► Methomyl induced DNA damage and apoptosis in Drosophila S2, HEK293 and HeLa cells. ► Methomyl induced DNA damage via both alkaline comet assay and γH2AX foci formation. ► Methomyl induced the apoptosis-associated DNA fragmentation. Carbamate insecticide methomyl could induce genotoxic effects, including micronuclei, chromosome aberrations and sister-chromatid exchanges. However, methomyl induction of cytotoxicity through DNA damage is largely unknown. Here we identify cytotoxicity and potential genotoxicity of methomyl in vitro. We have employed alkaline comet assay, γH2AX foci formation and DNA ladder assay to detected DNA damage and apoptosis of Drosophila S2, HeLa and HEK293 cells. The alkaline comet assay was used to evaluate total DNA single strand breaks (SSBs) in the target cells exposed in vitro to sublethal concentrations of methomyl. As expected, methomyl induced significant concentration-dependent increases in DNA damage of target cells compared with the negative control, as measured by increases in tail length (μm), tail DNA (percentage of the comet tail) and tail moment (arbitrary units). In agreement with the comet assay data, the percentage of γH2AX positive reaction in HeLa cells also revealed methomyl caused DNA double strand breaks (DSBs) in a time-dependent manner. Moreover, methomyl induced a significant increase of apoptosis in Drosophila S2, HeLa and HEK293 cells in a concentration- and time-dependent manner, as determined by Urea PAGE DNA fragmentation analysis. In conclusion, methomyl is a strongly genotoxic agent that induces cell DNA damage and apoptosis in vitro at these sublethal concentrations.