Mecanismos de carcinogênese induzidos por agrotóxicos: revisão sistemática
DOI:
https://doi.org/10.48075/aes.v5i1.27667Palavras-chave:
câncer de mama, carcinogênese, pesticidasResumo
A exposição crônica a pesticidas e desreguladores endócrinos causam alterações na expressão gênica em tecido mamário, o que torna mulheres submetidas a essa condição mais propicias a desenvolverem o câncer de mama. Este estudo teve como objetivo investigar e revisar sistematicamente a correlação entre exposição aos agrotóxicos e a carcinogênese mamária, apontando mecanismos observados in vivo e in situ. Foi utilizado o protocolo Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA), a busca foi realizada no PubMed, resultando em 58 artigos, incluídos no presente estudo. Diante do exposto pode-se observar genotoxicidade celular mediado pela exposição a pesticidas de diferentes classes químicas e desreguladores endócrinos, o que em tese desencadeiam o estresse genotóxico em tecido mamário normal promovendo a carcinogênese, e naquelas já diagnosticadas com câncer de mama levam a maior probabilidade de desenvolverem metástases. A presente revisão destaca a necessidade de estudos que explorem e identifiquem os mecanismos envolvidos em tal condição, sendo que evidências inequívocas relacionam a carcinogênese mamária com exposição a compostos químicos e desreguladores endócrinos.
Referências
Blondell JM. Pesticides and breast cancer, popcorn and colorectal cancer: Innovation versus fashion in dietary epidemiology. Medical Hypotheses. outubro de 1983;12(2):191–4.
Phrakonkham P, Brouland JP, Saad HES, Bergès R, Pimpie C, Pocard M, et al. Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model. Reproductive Toxicology. julho de 2015;54:101–9.
Gearhart-Serna LM, Hoffman K, Devi GR. Environmental Quality and Invasive Breast Cancer. Cancer Epidemiol Biomarkers Prev. outubro de 2020;29(10):1920–8.
Ortega Jacome GP, Koifman RJ, Rego Monteiro GT, Koifman S. Environmental Exposure and Breast Cancer Among Young Women in Rio De Janeiro, Brazil. Journal of Toxicology and Environmental Health, Part A. 28 de maio de 2010;73(13–14):858–65.
Yadava N, Schneider SS, Jerry DJ, Kim C. Impaired Mitochondrial Metabolism and Mammary Carcinogenesis. J Mammary Gland Biol Neoplasia. março de 2013;18(1):75–87.
Pestana D, Teixeira D, Faria A, Domingues V, Monteiro R, Calhau C. Effects of environmental organochlorine pesticides on human breast cancer: Putative involvement on invasive cell ability: Organochlorine Effects on Human Breast Cancer. Environ Toxicol. fevereiro de 2015;30(2):168–76.
Kalantzi OI. Low dose induction of micronuclei by lindane. Carcinogenesis. 24 de outubro de 2003;25(4):613–22.
Snedeker SM. Chemical Exposures in the Workplace: Effect on Breast Cancer Risk among Women. AAOHN Journal. junho de 2006;54(6):270–81.
Calaf G, Bleak T, Roy D. Signs of carcinogenicity induced by parathion, malathion, and estrogen in human breast epithelial cells (Review). Oncol Rep. 11 de fevereiro de 2021;45(4):24.
Birnbaum LS, Fenton SE. Cancer and developmental exposure to endocrine disruptors. Environ Health Perspect. abril de 2003;111(4):389–94.
Liu Y, Geng Y-H, Yang H, Yang H, Zhou Y-T, Zhang H-Q, et al. Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts. Cancer Letters. agosto de 2018;430:1–10.
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 21 de julho de 2009;6(7):e1000097.
Eldakroory S, Morsi DE, Abdel-Rahman R, Roshdy S, Gouida M, Khashaba E. Correlation between toxic organochlorine pesticides and breast cancer. Hum Exp Toxicol. dezembro de 2017;36(12):1326–34.
L’Héritier F, Marques M, Fauteux M, Gaudreau L. Defining Molecular Sensors to Assess Long-Term Effects of Pesticides on Carcinogenesis. IJMS. 25 de setembro de 2014;15(9):17148–61.
Wong PS, Li W, Vogel CF, Matsumura F. Characterization of MCF mammary epithelial cells overexpressing the Arylhydrocarbon receptor (AhR). BMC Cancer. dezembro de 2009;9(1):234.
Landau-Ossondo M, Rabia N, Jos-Pelage J, Marquet LM, Isidore Y, Saint-Aimé C, et al. Why pesticides could be a common cause of prostate and breast cancers in the French Caribbean Island, Martinique. An overview on key mechanisms of pesticide-induced cancer. Biomedicine & Pharmacotherapy. julho de 2009;63(6):383–95.
Wolff MS, Collman GW, Barrett JC, Huff J. Breast Cancer and Environmental Risk Factors: Epidemiological and Experimental Findings. :24.
Rivero J, Henríquez-Hernández LA, Luzardo OP, Pestano J, Zumbado M, Boada LD, et al. Differential gene expression pattern in human mammary epithelial cells induced by realistic organochlorine mixtures described in healthy women and in women diagnosed with breast cancer. Toxicology Letters. março de 2016;246:42–8.
Djordjevic MV, Hoffmann D, Fan J, Prokopczyk B, Citron ML, Stellman SD. Assessment of chlorinated pesticides and polychiorinated biphenyls in adipose breast tissue using a supercritical fluid extraction method. Carcinogenesis. 1994;15(11):2581–5.
Pontillo CA, García MA, Peña D, Cocca C, Chiappini F, Alvarez L, et al. Activation of c-Src/HER1/STAT5b and HER1/ERK1/2 Signaling Pathways and Cell Migration by Hexachlorobenzene in MDA-MB-231 Human Breast Cancer Cell Line. Toxicological Sciences. abril de 2011;120(2):284–96.
Miret NV, Pontillo CA, Zárate LV, Kleiman de Pisarev D, Cocca C, Randi AS. Impact of endocrine disruptor hexachlorobenzene on the mammary gland and breast cancer: The story thus far. Environmental Research. junho de 2019;173:330–41.
Pontillo C, Español A, Chiappini F, Miret N, Cocca C, Alvarez L, et al. Hexachlorobenzene promotes angiogenesis in vivo, in a breast cancer model and neovasculogenesis in vitro, in the human microvascular endothelial cell line HMEC-1. Toxicology Letters. novembro de 2015;239(1):53–64.
Peña D, Pontillo C, García MA, Cocca C, Alvarez L, Chiappini F, et al. Alterations in c-Src/HER1 and estrogen receptor α signaling pathways in mammary gland and tumors of hexachlorobenzene-treated rats. Toxicology. março de 2012;293(1–3):68–77.
Randi AS, Cocca C, Carbone V, Nuñez M, Croci M, Gutiérrez A, et al. Hexachlorobenzene Is a Tumor Co-carcinogen and Induces Alterations in Insulin-Growth Factors Signaling Pathway in the Rat Mammary Gland. Toxicological Sciences. 1o de janeiro de 2006;89(1):83–92.
Djordjevic MV, Fan J, Hoffmann D. Assessment of chlorinated pesticide residues in cigarette tobacco based on supercritical fluid extraction and GC-ECD. Carcinogenesis. 1995;16(11):2627–32.
Desaulniers D, Leingartner K, Russo J, Perkins G, Chittim BG, Archer MC, et al. Modulatory effects of neonatal exposure to TCDD, or a mixture of PCBs, p,p’-DDT, and p-p’-DDE, on methylnitrosourea-induced mammary tumor development in the rat. Environmental Health Perspectives. julho de 2001;109(7):739–47.
Imaida K, Shirai T. [Endocrine disrupting chemicals and carcinogenesis--breast, testis and prostate cancer]. Nihon Rinsho. dezembro de 2000;58(12):2527–32.
Cohn BA, Cirillo PM, La Merrill MA. Correlation of body mass index with serum DDTs predicts lower risk of breast cancer before the age of 50: prospective evidence in the Child Health and Development Studies. J Expo Sci Environ Epidemiol. maio de 2019;29(3):302–9.
Irigaray P, Newby JA, Lacomme S, Belpomme D. Overweight/obesity and cancer genesis: More than a biological link. Biomedicine & Pharmacotherapy. dezembro de 2007;61(10):665–78.
Dees C, Askari M, Garrett S, Gehrs K, Henley D, Ardies CM. Estrogenic and DNA-damaging activity of Red No. 3 in human breast cancer cells. Environmental Health Perspectives. 1997;105(3):8.
Dees C, Askari M, Foster JS, Ahamed S, Wimalasena J. DDT mimicks estradiol stimulation of breast cancer cells to enter the cell cycle. :8.
Choi K-C. Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway. Int J Mol Med [Internet]. 3 de fevereiro de 2012 [citado 19 de maio de 2021]; Disponível em: http://www.spandidos-publications.com/10.3892/ijmm.2012.903
Burow ME, Tang Y, Collins-Burow1 BM, Krajewski S, Reed JC, McLachlan JA, et al. Effects of environmental estrogens on tumor necrosis factor α-mediated apoptosis in MCF-7 cells. Carcinogenesis. novembro de 1999;20(11):2057–61.
Aubé M, Larochelle C, Ayotte P. 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p’-DDE) disrupts the estrogen-androgen balance regulating the growth of hormone-dependent breast cancer cells. Breast Cancer Res. fevereiro de 2008;10(1):R16.
Tessier DM, Matsumura F. Increased ErbB-2 Tyrosine Kinase Activity, MAPK Phosphorylation, and Cell Proliferation in the Prostate Cancer Cell Line LNCaP following Treatment by Select Pesticides. Toxicological Sciences. 1o de março de 2001;60(1):38–43.
Kalinina TS, Kononchuk VV, Gulyaeva LF. Expression of estrogen-, progesterone-, and androgen-responsive genes in MCF-7 and MDA-MB-231 cells treated with o,p’-DDT, p,p’-DDT, or endosulfan. J Biochem Mol Toxicol. 16 de março de 2021;e22773.
Zou E, Matsumura F. Long-term exposure to β-hexachlorocyclohexane (β-HCH) promotes transformation and invasiveness of MCF-7 human breast cancer cells. Biochemical Pharmacology. setembro de 2003;66(5):831–40.
Jaga K. What are the implications of the interaction between DDT and estrogen receptors in the body? Medical Hypotheses. janeiro de 2000;54(1):18–25.
Ventura C, Nieto MRR, Bourguignon N, Lux-Lantos V, Rodriguez H, Cao G, et al. Pesticide chlorpyrifos acts as an endocrine disruptor in adult rats causing changes in mammary gland and hormonal balance. The Journal of Steroid Biochemistry and Molecular Biology. fevereiro de 2016;156:1–9.
Bonefeld Jorgensen E. Effect of toxaphene on estrogen receptor functions in human breast cancer cells. Carcinogenesis. 1o de agosto de 1997;18(8):1651–4.
Starek A. Estrogens and organochlorine xenoestrogens and breast cancer risk. Int J Occup Med Environ Health. 2003;16(2):113–24.
Tsuda H. Carcinogenesis and Its Modification by Environmental Endocrine Disruptors: In Vivo Experimental and Epidemiological Findings. Japanese Journal of Clinical Oncology. 1o de junho de 2003;33(6):259–70.
Cargouët M, Bimbot M, Levi Y, Perdiz D. Xenoestrogens modulate genotoxic (UVB)-induced cellular responses in estrogen receptors positive human breast cancer cells. Environmental Toxicology and Pharmacology. julho de 2006;22(1):104–12.
Badawi AF, Cavalieri EL, Rogan EG. Effect of chlorinated hydrocarbons on expression of cytochrome P450 1A1, 1A2 and 1B1 and 2- and 4-hydroxylation of 17β-estradiol in female Sprague–Dawley rats. :7.
Lasagna M, Hielpos MS, Ventura C, Mardirosian MN, Martín G, Miret N, et al. Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells. Ecotoxicology and Environmental Safety. dezembro de 2020;205:111312.
Calaf G, Ponce‑Cusi R, Aguayo F, Mu�oz J, Bleak T. Endocrine disruptors from the environment affecting breast cancer (Review). Oncol Lett [Internet]. 22 de abril de 2020 [citado 19 de maio de 2021]; Disponível em: http://www.spandidos-publications.com/10.3892/ol.2020.11566
Calaf G, Roy D. Cancer genes induced by malathion and parathion in the presence of estrogen in breast cells. Int J Mol Med [Internet]. 1o de fevereiro de 2008 [citado 19 de maio de 2021]; Disponível em: http://www.spandidos-publications.com/10.3892/ijmm.21.2.261
Cabello G, Juarranz A, Botella LM, Calaf GM. Organophosphorous pesticides in breast cancer progression. J Submicrosc Cytol Pathol. janeiro de 2003;35(1):1–9.
Calaf. Organophosphorous pesticides and estrogen induce transformation of breast cells affecting p53 and c-Ha-ras genes. Int J Oncol [Internet]. 15 de setembro de 2009 [citado 19 de maio de 2021];35(05). Disponível em: http://www.spandidos-publications.com/ijo/35/5/1061
Cabello G, Valenzuela M, Vilaxa A, Durán V, Rudolph I, Hrepic N, et al. A rat mammary tumor model induced by the organophosphorous pesticides parathion and malathion, possibly through acetylcholinesterase inhibition. Environmental Health Perspectives. 2001;109(5):9.
Calaf GM, Roy D. Gene and Protein Expressions Induced by 17β-estradiol and Parathion in Cultured Breast Epithelial Cells. Mol Med. maio de 2007;13(5–6):255–65.
Calaf GM, Roy D. Cell adhesion proteins altered by 17ß estradiol and parathion in breast epithelial cells. ONCOLOGY REPORTS. 2008;5.
Calaf G, Roy D. Gene expression signature of parathion-transformed human breast epithelial cells. Int J Mol Med [Internet]. 1o de maio de 2007 [citado 19 de maio de 2021]; Disponível em: http://www.spandidos-publications.com/10.3892/ijmm.19.5.741
Calaf GM, Echiburú-Chau C. Synergistic effect of malathion and estrogen on mammary gland carcinogenesis. Oncology Reports. agosto de 2012;28(2):640–6.
Calaf G, Bleak T, Muñoz J, Aguayo F. Markers of epithelial-mesenchymal transition in an experimental breast cancer model induced by organophosphorous pesticides and estrogen (Review). Oncol Lett. 5 de agosto de 2020;20(4):1–1.
Go V, Garey J, Wolff MS, Pogo BGT. Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line. Environmental Health Perspectives. 1999;107(3):5.
Andrade FHE, Figueiroa FC, Bersano PRO, Bissacot DZ, Rocha NS. Malignant mammary tumor in female dogs: environmental contaminants. Diagn Pathol. 2010;5(1):45.
Perdichizzi S, Mascolo MG, Silingardi P, Morandi E, Rotondo F, Guerrini A, et al. Cancer-related genes transcriptionally induced by the fungicide penconazole. Toxicology in Vitro. fevereiro de 2014;28(1):125–30.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2022 Acta Elit Salutis
Este trabalho está licenciado sob uma licença Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Aviso de Direito Autoral Creative Commons
Política para Periódicos de Acesso Livre
Autores que publicam nesta revista concordam com os seguintes termos:
1. Autores mantém os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.2. Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.
3. Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado (Veja O Efeito do Acesso Livre).
Licença Creative Commons
Esta obra está licenciada com uma Licença Creative Commons Atribuição-NãoComercial-CompartilhaIgual 4.0 Internacional, o que permite compartilhar, copiar, distribuir, exibir, reproduzir, a totalidade ou partes desde que não tenha objetivo comercial e sejam citados os autores e a fonte.
