title: Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus.
abstract: Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells.
authors.affiliation: Laboratório de Toxicologia e Oncologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: D C M
authors.initials: DC
authors.lastname: Rapozo
authors.affiliation: Laboratório de Toxicologia e Oncologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: T C M
authors.initials: TC
authors.lastname: Blanco
authors.affiliation: Divisão de Patologia, Instituto Nacional de Câncer, Brazil.
authors.forename: B B
authors.initials: BB
authors.lastname: Reis
authors.affiliation: Laboratório de Toxicologia e Oncologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: I M
authors.initials: IM
authors.lastname: Gonzaga
authors.affiliation: Divisão de Patologia, Instituto Nacional de Câncer, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Valverde
authors.affiliation: Programa de Imunologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Canetti
authors.affiliation: Departamento de Biologia Celular, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Barja-Fidalgo
authors.affiliation: Laboratório de Toxicologia e Oncologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: T A
authors.initials: TA
authors.lastname: Simao
authors.affiliation: Laboratório de Toxicologia e Oncologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: R M
authors.initials: RM
authors.lastname: Albano
authors.affiliation: Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: C D P
authors.initials: CD
authors.lastname: Kruel
authors.affiliation: Laboratório de Toxicologia e Oncologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil; Programa de Carcinogênese Molecular, CPQ, Instituto Nacional de Câncer, Brazil. Electronic address: lfrpinto@inca.gov.br.
authors.forename: L F Ribeiro
authors.initials: LF
authors.lastname: Pinto
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity; D060766:Drinking Water / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006358:Hot Temperature; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008807:Mice, Inbred BALB C; D011230:Precancerous Conditions / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D060766:Drinking Water; D019394:Ki-67 Antigen; D004052:Diethylnitrosamine
keywords: Animal experimental model; Esophagus; Inflammation; Nitrosamines; Thermal lesion