Genes do fuso mitótico e ponto de checagem mitótico como biomarcadores da exposição ocupacional a agrotóxicos

Abstract

Pesticides are chemicals used indiscriminately in Brazil to control pests in agricultural crops. These products are classified into herbicides, insecticides and fungicides and can accumulate in the environment. A large number of epidemiological studies in rural workers have suggested a strong association with the increased risk of cancer in the group exposed to these compounds due to their genotoxic properties. Genes related to cell cycle regulation mechanisms (CDKN1A), mitotic checkpoint (MAD2 and CDC20) and mitotic spindle (AURKA, AURKB) are directly related to chromosomal stability and the development of neoplasms. The aim of this study is to evaluate the levels of expression of these genes in rural workers exposed to pesticides. This is the first study to assess these changes using bone marrow cells collected by spinal cord aspiration from rural workers exposed to pesticides. The analysis of gene expression was performed using the real-time PCR methodology, using bone marrow samples from 95 rural workers exposed to pesticides, divided into three groups: large producers, family farming and ecological farming. After analyzing gene expression, we identified that: farmers with 21 to 30 years of exposure to pesticides show an increase in expression of the AURKA gene when compared to farmers exposed between 1 to 10 years to pesticides (p = 0.041); the AURKB gene had reduced expression in farmers who used herbicide compared to individuals who did not (p = 0.049); farmers who have direct exposure to pesticides also show a decrease in the expression of AURKB when compared to farmers with indirect exposure to pesticides (p = 0.002); big farmers (p <0.000) and family farmers (p <0.000) (both use pesticides in their crops) showed MAD2 expression increased when compared to ecologically grown farmers (p = 0.049); Ecologically cultivated farmers showed increased expression of CDKN1A gene when compared to individuals with high production (p <0.000) and family farming (p <0.000). Through this study we hypothesized that the CDC20 and CDKN1A genes may correspond to new molecular markers for chronic occupational exposure to pesticides and we demonstrate that the genes related to the control of the cell cycle have uncontrolled expression in individuals exposed to pesticides. These results support the importance of the AURKA, AURKB, MAD2, CDC20 and CDKN1A genes to maintain the genomic stability of hematopoietic stem cells and may be involved in the process of carcinogenesis in the studied population.