Toxicoproteomics Disclose Pesticides as Downregulators of TNF-α, IL-1β and Estrogen Receptor Pathways in Breast Cancer Women Chronically Exposed

Abstract

Deleterious effects have been widely associated with chronic pesticide exposure, including cancer development. In spite of several known consequences that pesticides can trigger in the human body, few is known regarding its impact on breast cancer women that are chronically exposed to such substances during agricultural work lifelong. In this context, the present study performed a high-throughput toxicoproteomic study in association with a bioinformatics-based design to explore new putative processes and pathways deregulated by chronic pesticide exposure in breast cancer patients. To reach this goal, we analyzed comparatively non-depleted plasma samples from exposed (n = 130) and non-occupationally exposed (n = 112) women diagnosed with breast cancer by using a label-free proteomic tool. The list of proteins differentially expressed was explored by bioinformatics and the main pathways and processes further investigated. The toxicoproteomic study revealed that women exposed to pesticides exhibited mainly downregulated events, linked to immune response, coagulation and estrogen-mediated events in relation to the unexposed ones. Further investigation shown that the identified deregulated processes and pathways correlated with significant distinct levels tumor necrosis factor alpha and interleukin 1 beta in the blood, and specific clinicopathological characteristics pointed out by bioinformatics analysis as adipose-trophic levels, menopause and intratumoral clots formation. Altogether, these findings reinforce pesticides as downregulators of several biological process and highlight that these compounds can be linked to poor prognosis in breast cancer.

Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

“…Furthermore, pesticide exposure has already been shown to deregulate the inflammatory and immunological axis in occupationally exposed patients diagnosed with breast cancer, including systemic depletion of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), both pivotal anti-tumor cytokines [ 12 ]. It is well known that inflammation is a hallmark of cancer [ 13 ], and its deregulation by pesticides may bring relevant consequences to tumor progression.…”

Determination of glyphosate in breast milk of lactating women in a rural area from Paraná state, Brazil

“…Also, our findings indicated glyphosate residues in water samples from the same region of breastfeeding women, suggesting that environmental contamination could contribute in part to the pesticide load in human milk. Considering that the impact of pesticides on health has been documented in Brazilian studies from the same geographical area (26)(27)(28) and global efforts to support infant breastfeeding (29,30), these findings contribute significantly to this issue. Monitoring actions are necessary for this population since the consequences of glyphosate in child development are unclear.…”

Impact of Pesticides on Human Health in the Last Six Years in Brazil

“…Data from hematological tests of rural workers from the Southeast and South Brazilian regions exposed to organochlorines (OCs) and dithiocarbamate pesticides show hematological alterations, such as neutrophilia [ 117 ] or leucopenia [ 118 , 119 ]. The impact of chronic exposure to multiple pesticides was described in the immune response, showing in the plasma of exposed farmers compared to controls increased levels of the pro-inflammatory cytokines such IL-6 [ 105 ] and IL-1β and TNF-α [ 120 ], and augmented levels of C3, a key component in complement activation, amplification, and effector generation [ 119 ].…”