Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer
Abstract Rural women are at a higher risk of developing breast cancer, but the molecular mechanisms involved remain poorly understood. This study investigates the impact of chronic pesticide exposure on systemic and tissue-level protein expressions in women diagnosed with breast cancer. Plasma and t...
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| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-12870-2 |
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| author | Juliana Maria Bitencourt de Morais Valentim Luciana Pizzatti Carolina Coradi Isabella Cristina Cazagranda Bruna Fadel Beatriz Geovana Leite Vacario Shaiane Carla Gaboardi Matheus Iago Oliveira Coletto Rodrigo Kern Wander Rogério Pavanelli Daniel Rech Maria Luiza Ferreira dos Santos Leonardo Foti Allan Henrique Depieri Cataneo Guilherme Ferreira Silveira Juliano Bordignon Fábio Rodrigues Ferreira Seiva Carolina Panis |
| author_facet | Juliana Maria Bitencourt de Morais Valentim Luciana Pizzatti Carolina Coradi Isabella Cristina Cazagranda Bruna Fadel Beatriz Geovana Leite Vacario Shaiane Carla Gaboardi Matheus Iago Oliveira Coletto Rodrigo Kern Wander Rogério Pavanelli Daniel Rech Maria Luiza Ferreira dos Santos Leonardo Foti Allan Henrique Depieri Cataneo Guilherme Ferreira Silveira Juliano Bordignon Fábio Rodrigues Ferreira Seiva Carolina Panis |
| author_sort | Juliana Maria Bitencourt de Morais Valentim |
| collection | DOAJ |
| description | Abstract Rural women are at a higher risk of developing breast cancer, but the molecular mechanisms involved remain poorly understood. This study investigates the impact of chronic pesticide exposure on systemic and tissue-level protein expressions in women diagnosed with breast cancer. Plasma and tumor samples were collected from 215 women diagnosed with breast cancer; among them, 128 patients were occupationally exposed (n = 128) and 87 patients were not occupationally exposed (87) were analyzed for further studies. High-throughput proteomic analyses of plasma revealed distinct protein expression profiles between the groups, primarily associated with inflammation, oxidative stress, and immune deregulation. Validation analysis showed that cytokines such as IL-1β, IL-12, IL-17A, and TNF-α were significantly reduced in both plasma and tumor samples from exposed patients compared to unexposed women. This reduction in cytokines, coupled with decreased tumor-infiltrating leukocytes (TILs) and CTLA-4 overexpression, suggests pesticide-induced immune compromise. Circulating IL-12 levels were significantly reduced in younger, eutrophic, and at menacme exposed patients. Pesticide exposure also influenced nitrosative stress production, leading to reduced NOx levels in plasma and impaired iNOS expression in TILs. These results suggest a potential link between pesticide exposure and the pathophysiology of breast cancer, offering new insights into the underlying molecular mechanisms. |
| format | Article |
| id | doaj-art-3b7c0c86836c4232ab38b911398aff4a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3b7c0c86836c4232ab38b911398aff4a2025-08-24T11:20:58ZengNature PortfolioScientific Reports2045-23222025-08-0115111510.1038/s41598-025-12870-2Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancerJuliana Maria Bitencourt de Morais Valentim0Luciana Pizzatti1Carolina Coradi2Isabella Cristina Cazagranda3Bruna Fadel4Beatriz Geovana Leite Vacario5Shaiane Carla Gaboardi6Matheus Iago Oliveira Coletto7Rodrigo Kern8Wander Rogério Pavanelli9Daniel Rech10Maria Luiza Ferreira dos Santos11Leonardo Foti12Allan Henrique Depieri Cataneo13Guilherme Ferreira Silveira14Juliano Bordignon15Fábio Rodrigues Ferreira Seiva16Carolina Panis17Postgraduate Program in Experimental Pathology, State University of LondrinaLaboratory of Molecular Biology and Proteomics of Blood (LADETEC), Institute of Chemistry, Federal University of Rio de Janeiro, UFRJTumor Biology Laboratory, State University of Western Paraná, UNIOESTEGrupo de Imunologia Molecular, Celular e Inteligência Artificial- Instituto Carlos ChagasLaboratory of Molecular Biology and Proteomics of Blood (LADETEC), Institute of Chemistry, Federal University of Rio de Janeiro, UFRJPostgraduate Program in Molecular Genetics, State University of LondrinaCatarinense Federal Institute of Education, Science and TechnologyTumor Biology Laboratory, State University of Western Paraná, UNIOESTELaboratory of Molecular Biology and Proteomics of Blood (LADETEC), Institute of Chemistry, Federal University of Rio de Janeiro, UFRJPostgraduate Program in Experimental Pathology, State University of LondrinaTumor Biology Laboratory, State University of Western Paraná, UNIOESTEGrupo de Imunologia Molecular, Celular e Inteligência Artificial- Instituto Carlos ChagasPostgraduate Program in Molecular Genetics, State University of LondrinaLaboratório de Virologia Molecular, Instituto Carlos Chagas/Fiocruz-PRGrupo de Imunologia Molecular, Celular e Inteligência Artificial- Instituto Carlos ChagasGrupo de Imunologia Molecular, Celular e Inteligência Artificial- Instituto Carlos ChagasPostgraduate Program in Experimental Pathology, State University of LondrinaPostgraduate Program in Experimental Pathology, State University of LondrinaAbstract Rural women are at a higher risk of developing breast cancer, but the molecular mechanisms involved remain poorly understood. This study investigates the impact of chronic pesticide exposure on systemic and tissue-level protein expressions in women diagnosed with breast cancer. Plasma and tumor samples were collected from 215 women diagnosed with breast cancer; among them, 128 patients were occupationally exposed (n = 128) and 87 patients were not occupationally exposed (87) were analyzed for further studies. High-throughput proteomic analyses of plasma revealed distinct protein expression profiles between the groups, primarily associated with inflammation, oxidative stress, and immune deregulation. Validation analysis showed that cytokines such as IL-1β, IL-12, IL-17A, and TNF-α were significantly reduced in both plasma and tumor samples from exposed patients compared to unexposed women. This reduction in cytokines, coupled with decreased tumor-infiltrating leukocytes (TILs) and CTLA-4 overexpression, suggests pesticide-induced immune compromise. Circulating IL-12 levels were significantly reduced in younger, eutrophic, and at menacme exposed patients. Pesticide exposure also influenced nitrosative stress production, leading to reduced NOx levels in plasma and impaired iNOS expression in TILs. These results suggest a potential link between pesticide exposure and the pathophysiology of breast cancer, offering new insights into the underlying molecular mechanisms.https://doi.org/10.1038/s41598-025-12870-2PesticidesBreast cancerOxidative stressImmune responseImmune compromise |
| spellingShingle | Juliana Maria Bitencourt de Morais Valentim Luciana Pizzatti Carolina Coradi Isabella Cristina Cazagranda Bruna Fadel Beatriz Geovana Leite Vacario Shaiane Carla Gaboardi Matheus Iago Oliveira Coletto Rodrigo Kern Wander Rogério Pavanelli Daniel Rech Maria Luiza Ferreira dos Santos Leonardo Foti Allan Henrique Depieri Cataneo Guilherme Ferreira Silveira Juliano Bordignon Fábio Rodrigues Ferreira Seiva Carolina Panis Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer Scientific Reports Pesticides Breast cancer Oxidative stress Immune response Immune compromise |
| title | Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer |
| title_full | Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer |
| title_fullStr | Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer |
| title_full_unstemmed | Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer |
| title_short | Pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer |
| title_sort | pesticide exposome reveals oxidative stress and immune response disruptions in occupationally exposed women with breast cancer |
| topic | Pesticides Breast cancer Oxidative stress Immune response Immune compromise |
| url | https://doi.org/10.1038/s41598-025-12870-2 |
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