The Implications of Connexin 43 Deficiency during the Early Stages of Chemically Induced Mouse Colon Carcinogenesis

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorVrije Universiteit Brussel (VUB)-
Autor(es): dc.creatorSanto, Sara Gomes Espírito-
Autor(es): dc.creatorda Silva, Tereza Cristina-
Autor(es): dc.creatorVinken, Mathieu-
Autor(es): dc.creatorCogliati, Bruno-
Autor(es): dc.creatorBarbisan, Luís Fernando-
Autor(es): dc.creatorRomualdo, Guilherme Ribeiro-
Data de aceite: dc.date.accessioned2025-08-21T19:41:37Z-
Data de disponibilização: dc.date.available2025-08-21T19:41:37Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2022-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/antiox11122368-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/248100-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/248100-
Descrição: dc.descriptionColorectal cancer (CRC), associated with an increased intake of processed red meats, saturated fats, and simple carbohydrates accompanied by low dietary fiber, fruits, and vegetables consumption, presents a high epidemiological burden. Connexin43 (Cx43) protein, which forms gap junctions or hemichannels, has tumor suppressor or oncogenic activities in a cancer type- and stage-dependent manner. Cx43 expression varies during colon carcinogenesis, and its functional role is not fully understood. Thus, we evaluated the implications of Cx43 heterologous deletion (Cx43+/−) during the early stages of a chemically induced model of colon carcinogenesis. Female C57BL/6J mice (wild-type or Cx43+/−) were submitted to a colon carcinogenesis model induced by 1,2 dimethylhydrazine (DMH). Mice were euthanized eight hours (week 7) or 30 weeks (week 37) after the last DMH administration to evaluate subacute colon toxicity outcomes or the burden of (pre)neoplastic lesions, respectively. At week 7, Cx43 deficiency inferred no alterations in the DMH-induced increase in systemic (peripheral blood), in situ (colonocytes) DNA damage, and apoptosis in the colonocytes. At week 30, Cx43+/− mice presented an increase in preneoplastic aberrant crypt foci (ACF) multiplicity, while no alterations were observed in colorectal adenoma (CRA) occurrence, multiplicity, volume, proliferation, growth, and β-catenin immunoexpression. Similarly, an in silico analysis of human CRA showed decreased mRNA expression of Cx43 with no correlation with proliferation, apoptosis, and β-catenin markers. These findings indicate the discrete role of Cx43 in the early stages of chemically induced mouse colon carcinogenesis.-
Descrição: dc.descriptionDepartment of Pathology Botucatu Medical School São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionSchool of Veterinary Medicine and Animal Science University of São Paulo (USP), São Paulo-
Descrição: dc.descriptionDepartment of In Vitro Toxicology and Dermato-Cosmetology Vrije Universiteit Brussel (VUB)-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Botucatu Medical School São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionDepartment of Pathology Botucatu Medical School São Paulo State University (UNESP), São Paulo-
Descrição: dc.descriptionDepartment of Structural and Functional Biology Botucatu Medical School São Paulo State University (UNESP), São Paulo-
Idioma: dc.languageen-
Relação: dc.relationAntioxidants-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject1,2-dimethylhydrazine-
Palavras-chave: dc.subjectaberrant crypt foci-
Palavras-chave: dc.subjectC57BL/6J mouse-
Palavras-chave: dc.subjectcolon carcinogenesis-
Palavras-chave: dc.subjectcolorectal adenoma-
Palavras-chave: dc.subjectconnexin 43-
Título: dc.titleThe Implications of Connexin 43 Deficiency during the Early Stages of Chemically Induced Mouse Colon Carcinogenesis-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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