Gene expression profiling of proximal versus distal mouse colon during AOM/DSS-induced colitis-associated carcinogenesis.. Mus musculus

In humans with UC, low-grade dysplasia also develops predominantly in the distal colon, progresses more rapidly to neoplasia than proximal colon low-grade dysplasia and associates with worse patient prognosis. In a mouse model of colitis-associated carcinogenesis induced by administration of the mutagen AOM and the luminal toxin DSS, tumors also develop exclusively in the distal part of the large intestine. We monitored global changes in the transcriptome of mouse proximal and distal colon during exposure to AOM/DSS with the aim to define biological pathways and processes that characterize regional responses of the large intestine to colitis-associated carcinogenesis. Overall design: Female C57BL/6J mice were injected intaperitoneally with 10mg/kg body weight azoxymethane (AOM) when their weight was approximately 18-20 g (day 1) and 96 hours later 2.5% DSS was administered in their drinking water for five days, followed by 14 days of regular water. This cycle was repeated once (EARLY TREATMENT GROUP) or three times more (LATE TREATMENT GROUP) before mice were sacrificed on days 42 and 120 respectively. Macroscopic and histological analyses showed dysplasias and intramucosal adenocarcinomas in the distal colon of the late treatment group and areas of dysplasia in the early treatment group. The proximal part of the colon remained unaffected. At least three (3) animals (biological replicates) were used to isolate tissue from proximal and distal areas of the large intestine under different treatment conditions (early vs late AOM/DSS treatment and untreated controls) which was processed for RNA isolation and gene expression profiling.