Chronic inflammation (CI) such as inflammatory bowel disease (ulcerative colitis or Crohns disease) increases the risk of developing colorectal cancer (CRC). Inflammatory cytokines support inflammation-associated tumour promotion through increased cell proliferation, angiogenesis and inhibiting apoptosis of neoplastic cells. The classic mouse model of colitis-associated CRC (CA-CRC) requires treatment with a mutagen (typically azoxymethane, AOM) followed by induction of inflammation through ingestion of a luminal irritant (typically dextran sodium sulfate, DSS). AOM is metabolized by colonic epithelium causing DNA damage through formation of mutagenic DNA adducts. Although the AOM + DSS model of CA-CRC is a valuable research tool, it does “reverse” the events that take place in humans where CI precedes CRC.  We hypothesise that CI sensitises colonic epithelium to DNA damage and thus predisposes the epithelium to neoplastic transformation. In order to investigate this we reversed the AOM + DSS model to more representatively mimic disease progression in humans. Wildtype mice were exposed to DSS to induce a mild level of CI (to retain the capacity of the epithelium to metabolise AOM) before successive intraperitoneal AOM injections. We found that aberrant crypt foci (ACF) was significantly increased in the cohort that had received DSS prior to AOM compared to the cohort that had received AOM alone (2.6 fold increase, p<0.01). This data suggests a functional relationship between CI, subsequent exposure to mutagens and tumour development. Apoptosis and DNA damage will also be compared between cohorts. Accordingly this model should act as an experimental framework to better understand the molecular mechanisms underpinning CA-CRC.