Avaliação das alterações celulares e moleculares mediadas por pesticidas em células prostáticas humanas

Abstract

Brazil's economy is based on agricultural production, being one of the largest exporters of commodities worldwide. To this end, the country increased the quality and productivity of its crops, becoming an important consumer of pesticides, mainly Glyphosate (GLI) and its main by-product, Aminomethylphosphonic acid (AMPA). The exacerbated and/or frequent consumption of these substances has already been related to the development of several diseases.Therefore, the present study aimed to understand the modulation of events related to prostatic tumorigenesis mediated by the herbicides Glyphosate (GLI) and its main by-product, Aminomethylphosphonic acid (AMPA). Cell viability was initially evaluated by the MTT method in non-tumorigenic prostatic cells (PNT2), LNCaP (hormone-dependent PCa), and PC-3 (hormone-independent PCa). In PNT2 cells, the relative expression of the transcripts was analyzed by the qPCR method, and the proliferative capacity was verified by clonogenic assay. The expression of Glutathione Stransferase Mu3 (GSTM3), the enzymatic activity of GSTs, and protein oxidation were also determined. The results show that GLI and AMPA were cytotoxic after 48 hours of treatment and only at higher concentrations, mainly in the PNT2 lineage. On the other hand, these compounds increased colony formation, especially at concentrations below IC50 values (5 mM GLI and 10 mM AMPA). In this condition, there was an increase in transcriptional levels of the GSTM3 gene, as well as in its protein expression. However, GST enzymatic activity was significantly decreased, with an increase in oxidative stress. Therefore, GLI and AMPA can drive molecular changes in PNT2 cells, especially related to oxidative stress, even at non-cytotoxic concentrations. Additional studies are needed to better understand the effects of these herbicides, especially at residual concentrations.