DNA damage and epigenetic alteration in soybean farmers exposed to complex mixture of pesticides

Abstract

Exposure to pesticides can trigger genotoxic and mutagenic processes through different pathways. However, epidemiological studies are scarce, and further work is needed to find biomarkers sensitive to the health of exposed populations. Considering that there are few evaluations of soybean farmers, the aim of this study was to assess the effects of human exposure to complex mixtures of pesticides. The alkaline comet assay modified with restriction enzyme (hOGG1: human 8-oxoguanine DNA glycosylase) was used to detect oxidised guanine, and compared with the buccal micronucleus cytome assay, global methylation, haematological parameters, biochemical analyses (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma-glutamyl-transferase and butyrylcholinesterase), and particle-induced X-ray emission (PIXE) for the analysis of inorganic elements. Farm workers (n = 137) exposed to different types of pesticides were compared with a non-exposed reference group (control; n = 83). Results of the enzyme-modified comet assay suggest oxidation of guanine in DNA generated by pesticides exposure. It was observed that DNA damage (comet assay and micronucleus test) was significantly increased in exposed individuals compared to the unexposed group. The micronucleus test demonstrated elimination of nuclear material by budding, defective cytokinesis and dead cells. Occupationally exposed individuals also showed genomic hypermethylation of DNA, which correlated with micronucleus frequency. No differences were detected regarding the haematological and biochemical parameters. Finally, significantly higher concentrations of Al and P were observed in the urine of the soybean farmers. DNA damage could be a consequence of the ability of the complex mixture, including Al and P, to cause oxidative damage. These data indicate that persistent genetic instability associated with hypermethylation of DNA in soybean workers after long-term exposure to a low-level to pesticides mixtures may be critical for the development of adverse health effects such as cancer.

MGMT methylation alterations in brain cancer following organochlorine pesticides exposure

“…The present study also revealed that the patients who were farmers or engaged in agricultural activities were more likely to have methylation in the MGMT gene promoter. Accordingly, Benedetti et al demonstrated that long-term exposure to pesticides induced hypermethylation of DNA in soybean farmers which may be critical for the development of adverse health effects such as cancer (19). Furthermore, due to the high methylation frequencies of the MGMT promoter in glioma patients, this study also investigated the possible associations between methylation of the MGMT promoter and OCPs in the serum of those with gliomas.…”

Validation of exposure indexes to pesticides through the analysis of exposure and effect biomarkers in ground pesticide applicators from Argentina

“…A previous case-control study, carried out in Argentina, reported similar results, with higher cholinesterase activities in subjects within the OE group than in NOE, but without significant differences (Lerda and Masiero, 1990). Worldwide, many case/control studies describe no association between chronic low-doses exposure to pesticides and a drop in the cholinesterase activity (Adad et al, 2015;Benedetti et al, 2017;Oliveira et al, 2019). These results could be explained by induction of compensatory synthesis of the enzyme after long-term exposure to pesticides (Hernandez et al, 2005;Keller et al, 2001).…”

“…The occupational condition was the only, or the main, predictor variable influencing these differences. Increased genetic and epigenetic alterations are widely described in the OE population regarding the NOE population (Benedetti et al, 2017;Martinez-Valenzuela et al, 2017;Oliviera et al, 2019). These findings confirm the fact that pesticides, used by the OE subjects, are capable to induce genotoxic changes in this population, in addition to the cumulative effect that these alterations could produce, triggering chronic diseases.…”

Cytotoxicity as a Fundamental Response to Xenobiotics

“…In this sense, it has also been shown that exposure to pesticides can induce oxidative DNA damage, single and double breaks, and adduct formation [83]. Although there are different DNA repair mechanisms for these damages and for the maintenance of cellular integrity, excessive damage or irreparable damage can lead to cell death processes [8,83,84].…”