Caracterização de alterações inflamatórias no tecido mamário de mulheres agricultoras induzidas pela exposição ocupacional aos agrotóxicos

Abstract

According to the International Agency for Research on Cancer (IARC), pesticides are substances with high carcinogenic potential. Studies have documented the high occurrence of several tumors, including female breast cancer, in populations occupationally exposed to pesticides worldwide. It is still unclear how pesticides act as stimulators of breast carcinogenesis. It is believed that in addition to direct DNA damage, other molecular alterations that indicate genomic instability are associated, such as epigenetic modifications and the production of inflammation mediators. In this context, the present study characterized the profile of the inflammatory change in women without cancer occupationally exposed to pesticides in the breast tissue. A total of 102 women treated at Hospital do Câncer de Francisco Beltrão (CEONC), Paraná, Brazil, from May 2015 to August 2022, with negative biopsies and images for breast cancer, were included. The occupational exposure to pesticides was characterized using a validated instrument for this purpose. Women rural workers with a history of past and current direct contact with pesticides through the handling and preparation of the poison solution, spraying and/or decontamination, and washing of clothes and equipment used in applying pesticides without the use of protective gloves were considered exposed. (n=42). For the unexposed group, women from the urban area engaged in activities outside of agriculture were included, without contact with pesticides in the past or present (n=60). In samples of normal breast tissue collected during biopsy and evaluated as negative for cancer by a pathologist, the levels of oxidative stress were assessed as inflammatory markers through measurements of lipoperoxides and total antioxidant capacity of the sample (TRAP) by high-sensitivity chemiluminescence. , as well as the levels of nitric oxide (NOx) metabolites. The levels of the inflammation-modulating transcription factors PPAR-γ (peroxisome proliferator activated receptor gamma) and NF-κB (nuclear factor kappa B) were also quantified, in addition to the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α). ) and interleukin 12 (IL-12). The levels of lipoperoxides, TRAP, and NOx were significantly lower in the exposed group. On the other hand, PPAR-γ levels were increased in the breast tissue of exposed women, with no variation i n NF-κB. There was also a tissue increase in TNF-α in exposed women without significant variations in IL-12 levels. These findings suggest an inflammatory signature of breast tissue associated with pesticide exposure. The genomic instability generated by exposure to pesticides creates an environment of sustained inflammation evidenced by the body's defense response to oxidative stress (OS), concomitant with the reduction of critical antitumor mechanisms, which may trigger mechanisms related to the occurrence of mutations and breast carcinogenesis.