br Conflict of interest br Acknowledgements This work was
Conflict of interest
Acknowledgements This work was partially supported by University of Cagliari.
Introduction Organophosphorous pesticides (OPs) are wildly used in the world due to high efficiency, broad spectrum and low residue, which in turn results in environmental pollution and adverse health effects (Duan et al., 2017, Parker et al., 2017). Inhibiting cholinesterases (ChEs) activity is the primary toxicity mechanisms of OPs, which leads to immediate neurotoxic effects and delayed effects, including neurodegenerative diseases and effects on children exposed in utero (Peres et al., 2016; Quandt et al., 2015; Ridano et al., 2017). DNA damage and ChEs activity were used as biomarkers of acute and chronic effects of exposure to OPs. Telomere binding proteins (TBPs) locate at the end of the 6015 mass and are closely related to chromosome stability. Genomic stability is mainly mediated by protein complexes recruited to telomeric sequences by specific TBPs (Cervenak et al., 2017). DNA damage is one of the major molecular events in malignant transformation. Telomere DNA is in the chromosome end. Therefore, telomere is likely more vulnerable to attack from external intruders. Due to the problem of DNA replication to the ends of linear chromosomes, telomere DNA shortens at a speed of 50–200 bp during the cell replication process (Zhao et al., 2009). TBPs might involve in the DNA shortening process due to binding to telomere DNA. TBPs related genes include telomeric repeat binding factors (TERF1 and TERF2), protection of telomeres protein 1(POT1), human repressor activator protein 1 (RAP1), and other proteins (Mucciardi et al., 2014). TERF1 can directly identify the telomeres TTAGGG repeats, and its main function is to negatively adjust telomere DNA length by inhibiting telomerase activity (Patel et al., 2015). POT1 gene plays an important role in telomere homeostasis through extending the telomere by activating telomerase, and it also prevents telomerase-dependence telomere extension by isolating the telomeres 3′ hanging end and maintaining telomeres T loop structure with the cooperation with TERF1 and TRF2 (Loayza and de Lange, 2003, Yang et al., 2005). TERT is one of the subunits of telomerase and evidence has shown that somatic gain-of-function mutations in the TERT promoter promote the transcriptional activity of TERT which subsequently maintain telomere length in human cancers (Gao et al., 2016). Telomeres pathway genes POT1, TERF1 and TERT play a key role in maintain chromosomal stability. TBPs participate in cell differentiation, senescence and death (Hosokawa and Arai, 2018). There are possibly two main pathways for the changes in ChEs. Firstly, tissue homeostasis requires an orchestrated balance between cell proliferation and cellular senescence (Schmitt et al., 2007). An appropriate telomere maintenance system is necessary for cell replicative potential (Patel et al., 2015), critically short telomeres elicit a DNA damage associated with cell cycle arrest and replicative senescence (O\'Sullivan and Karlseder, 2010). DNA-damage reparation genes and telomere maintenance genes are involved in the DNA repairing process. Therefore, the TBPs could affect the quantity and quality of peripheral red blood cells which could influence the ChEs (van der Harst et al., 2012). Secondly, the TBPs can affect chromosomal stability, and then change the expression levels of cholinesterase-related genes, and thus affect the production and degradation of cholinesterase. Omethoate is one of the OPs, which is widely used in China. Our previous study shows that the relative telomere lengths in the omethoate exposure group were significantly longer than that in the control group. The genetic polymorphisms in cell-cycle-regulating genes including p53 and p21 may influence the DNA damage (Duan et al., 2017). Recently, there are a large body of studies suggested that polymorphisms of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 are closely related to chromosome stability and cancers (Cheng et al., 2017, Yuan et al., 2017). TBPs gene polymorphisms influence the stability of chromosome. Genetic susceptibility is different in individuals who are exposed to OPs. So far, there are few studies on the correlations between the polymorphisms of POT1, TERF1, TERT gene and ChEs activities.