Wang Chao, Zhang Ziwei, Yao Haidong, Zhao Fuqing, Wang Liangliang, Wang Xiaolong, Xing Houjuan, Xu Shiwen
Department of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
Center of conservation medicine & ecological safety, Northeast Forestry University, Harbin, 150040, PR China.
Ecotoxicol Environ Saf. 2014 Oct;108:142-51. doi: 10.1016/j.ecoenv.2014.06.011. Epub 2014 Jul 23.
Pesticide exposure has repeatedly been associated with cancers, although the molecular mechanisms behind this association are largely undetermined. Abnormal DNA methylation plays a key role in the process of some disease. However, little was known about the effect of pesticides on DNA methylation in the common carp. In this study, we investigated the mRNA levels of DNA methyltransferases (DNMTs) and methyl-CpG-binding protein DNA-binding domain protein 2 (MBD2) as well as the DNA methylation levels in the liver, kidney and gill of the common carp (Cyprinus carpio L.) after 40-d exposure to atrazine (ATR) and chlorpyrifos (CPF) alone or in combination, and a 40-d recovery period. Juvenile common carp were exposed to various concentrations of ATR (at concentrations of 4.28, 42.8 and 428μg/L), CPF (1.16, 11.6 and 116μg/L), and an ATR/CPF mixture (at concentrations of 1.13, 11.3 and 113μg/L). The results revealed that the levels of genomic DNA methylation decreased in all tissues after 40d of exposure to ATR and CPF either individually or in combination. Moreover, the mRNA expression of DNMTs was down-regulated in all treatment groups. In contrast, the mRNA expression of MBD2 was up-regulated. These results demonstrated that long-term exposure to ATR, CPF and ATR/CPF mixtures could disrupt genomic DNA. It might imply that DNA methylation is involved in the toxicity caused by ATR and CPF in the common carp.
农药暴露一再被证实与癌症有关,尽管这种关联背后的分子机制在很大程度上尚未明确。异常的DNA甲基化在某些疾病的发生过程中起着关键作用。然而,关于农药对鲤鱼DNA甲基化的影响却知之甚少。在本研究中,我们调查了鲤鱼(Cyprinus carpio L.)在单独或联合暴露于莠去津(ATR)和毒死蜱(CPF)40天以及40天恢复期后,其肝脏、肾脏和鳃中DNA甲基转移酶(DNMTs)和甲基-CpG结合蛋白DNA结合结构域蛋白2(MBD2)的mRNA水平以及DNA甲基化水平。将幼鲤暴露于不同浓度的ATR(浓度分别为4.28、42.8和428μg/L)、CPF(1.16、11.6和116μg/L)以及ATR/CPF混合物(浓度分别为1.13、11.3和113μg/L)中。结果显示,在单独或联合暴露于ATR和CPF 40天后,所有组织中的基因组DNA甲基化水平均下降。此外,所有处理组中DNMTs的mRNA表达均下调。相反,MBD2的mRNA表达上调。这些结果表明,长期暴露于ATR、CPF和ATR/CPF混合物会破坏基因组DNA。这可能意味着DNA甲基化参与了ATR和CPF对鲤鱼的毒性作用。