The Progressive Mutagenic Effects of Acidic Bile Refluxate in Hypopharyngeal Squamous Cell Carcinogenesis: New Insights.

ABSTRACT: Cancers of the laryngopharynx represent the most devastating of the head and neck malignancies and additional risk factors are now epidemiologically linked to this disease. Using an in vivo model (Musmusculus C57Bl/6J), we provide novel evidence that acidic bile (pH 3.0) progressively promotes invasive cancer in the hypopharynx. Malignant lesions are characterized by increasing: i) oxidative DNA-damage, ii) γH2AX expression, iii) NF-κB activation, and iv) p53 expression. Histopathological changes observed in murine hypopharyngeal mucosa exposed to acidic bile were preceded by the overexpression of Tnf, Il6, Bcl2, Egfr, Rela, Stat3, and the deregulation of miR-21, miR-155, miR-192, miR-34a, miR-375, andmiR-451a. This is the first study to document that acidic bile is carcinogenic in the upp

SUBMITTER: Sasaki CT 

PROVIDER: S-EPMC7281001 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature