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NDMA enhances claudin-1 and -6 expression viaCYP2E1/ROS in AGS cells.
García-García, Carlos Abraham; Cruz-Gregorio, Alfredo; Pedraza-Chaverri, José; Montaño, Luis F; Rendón-Huerta, Erika P.
Afiliação
  • García-García CA; Laboratorio de Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico.
  • Cruz-Gregorio A; Departamento de Fisiología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico.
  • Pedraza-Chaverri J; Departamento de Biología, Facultad de Química, UNAM, Mexico.
  • Montaño LF; Laboratorio de Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico.
  • Rendón-Huerta EP; Laboratorio de Inmunobiología, Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico. Electronic address: erendon@unam.mx.
Toxicol In Vitro ; 102: 105952, 2024 Oct 10.
Article em En | MEDLINE | ID: mdl-39395750
ABSTRACT
Carcinogenic N-nitroso compounds, especially N-nitroso dimethylamine, increase the risk of gastric cancer development. Cytochrome P450-2E1 metabolizes this compound, thus generating an oxidant microenvironment. We aimed to evaluate in gastric adenocarcinoma cells if its effect on CYP2E1 and ROS affects signaling pathways associated with gastric cancer oncogenesis. The impact of N- nitroso dimethylamine upon CYP2E1 and ROS activation/secretion was evaluated by the DCFDA assay protocol, TER measurements, Stat3, pSTAT3, ERK1/2, and pERK1/2 expression, claudins-1 and -6 expression, and finally mRNA values of IL-1ß IL-6, IL-8 and TNFα. Our results showed that exposure to N- N-nitroso dimethylamine disrupts the regulation of Stat3 and Erk1/2, alters the expression of claudin-1 and claudin-6 tight junction proteins, and increases the secretion of pro-inflammatory cytokines. These alterations induce a continuous local inflammatory process, an event identified as a gastric cancer promoter. In summary, N-nitroso dimethylamine can disrupt cell mechanisms associated with gastric cancer oncogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Toxicol In Vitro Assunto da revista: TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Toxicol In Vitro Assunto da revista: TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido