Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer

摘要

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the gastrointestinal tract that affects millions of people worldwide and significantly increases the risk of colon cancer. More than 20% of patients with IBD develop colitis-associated cancers within 30 y of onset (1). While dysregulation of host-microbiome interactions, genetic predisposition, and environment are associated with IBD (1, 2), the molecular and chemical mechanisms linking colonic inflammation with cancer have not been defined. Current models of inflammation-mediated carcinogenesis involve infiltration of activated phagocytes at sites of infection with subsequent generation of damaging reactive oxygen, nitrogen, and halogen species that lead to mutation, cell death, and cancer (3). To better understand colitis-associated carcinogenesis, we employed an established animal model of human IBD.