Changes in the expression of genes involved in cell cycle regulation and the relative telomere length in the process of canceration induced by omethoate

Abstract

Organophosphorous pesticides (OPs), with high efficiency, broad-spectrum and low residue, are widely used in China. Omethoate is a broad category of organophosphorous pesticides and is more domestically utilized which has chronic toxic effect on human health caused by long-term, low-dose exposure to Ops, recently its potential genotoxicity has attracted wide attention which can cause chromosomal DNA damage. Thus, the aim of this study is screen susceptible biomarkers and explore the mechanism of canceration induced by omethoate. 180 long-term organophosphorus pesticide-exposed workers and 115 healthy controls were recruited. Quantitative polymerase chain reaction method was applied to determine the relative telomere length in peripheral lymphocyte DNA as well as p53 and p21 gene expression levels. Genetic polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Multiple linear regression was conducted to explore the effects of exposure, expression levels, and polymorphisms in genes on the telomere length. The results showed the relative telomere lengths in the exposure group were significantly longer than that in the control group. The messenger RNA expression levels of p53 and p21 in exposure group were significantly lower than that in the control group; telomere lengths of the CA genotype individuals of p21 rs1801270 polymorphism locus were significantly longer than that of the CC genotype in the control group that were estimated using the Bonferroni method; and bivariate correlation analysis showed that the messenger RNA expression level of gene p53 was negatively correlated with telomere length, and the messenger RNA expression level of gene p21 was positively correlated with telomere length. Multivariate analysis found that p53 messenger RNA and p21 messenger RNA had an impact on telomere length. These results demonstrated that the messenger RNA expression levels of p53 and p21 may have a relationship with the changes in telomere length induced by omethoate and provided strong evidence for the mechanism of canceration induced by poison.

Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate

“…Second, the cell-cycle genes can affect chromosomal stability, and then affect the expression levels of cholinesterase-related genes, and thus affect the formation and degradation of cholinesterase. Previous studies have found that OP exposure can cause chromosomal DNA damage including telomere damage, DNA double- and single-strand breaks, chromosome aberration and micronucleus [ 6 , 9 , 32 , 33 ]. Therefore, this study investigated the effect of cell-cycle genes on ChA.…”

“…Six polymorphic loci of p53 rs1042522, p53 rs17878362, p53 rs1625895, p21 rs1801270, p21 rs1059234 and mdm2 rs3730485 from the three genes were detected using genomic DNA isolated from peripheral blood lymphocytes. For the detection method for genotyping, primer sequences and restriction endonucleases, the reader is referred to a previous publication by our group [ 9 ].…”

“…It has been shown that DNA damage could change the level of ChA through effects on the quantity and quality of red blood cells. When cells are damaged, cell division will stagnate in the G1 phase of mitosis, so the checkpoint is extremely important in this phase [ 9 ]. In cell-cycle checkpoint regulation, the arrest of the cell cycle in G1/S transition is a p53-dependent process [ 10 ].…”

Cross-sectional associations between genetic polymorphisms in metabolic enzymes and longer leukocyte telomere length induced by omethoate

“…Multiplex PCR were used to detect the deletion in GSTT1 and GSTM1 ; PCR-RFLP method was used to detect other loci for genotyping; primer sequences and restriction endonucleases were described previously [ 30 , 33 ]. The PCR and enzyme reaction conditions referred to the published paper in task group [ 34 ]; just in the experimental process of PCR, we should select a different annealing temperature depending on the Tm value and pre-experimental results.…”

Signs of carcinogenicity induced by parathion, malathion, and estrogen in human breast epithelial cells (Review)

“…p53 is another gene involved in the regulation of the cell cycle, serving as a checkpoint for the G 1 -S phase (75). At the same time, the MDM2 gene regulates p53 and is associated with tumor growth and metastasis (76).…”