10.6084/m9.figshare.11356808.v1 Lauren C. Chartier Lauren C. Chartier Gordon S. Howarth Gordon S. Howarth Suzanne Mashtoub Suzanne Mashtoub Chemotherapy-induced mucositis development in a murine model of colitis-associated colorectal cancer Taylor & Francis Group 2019 5-FU chemotherapy colitis-associated colorectal cancer cancer IBD mucositis mouse model 2019-12-11 23:43:04 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Chemotherapy-induced_mucositis_development_in_a_murine_model_of_colitis-associated_colorectal_cancer/11356808 <p><b>Objectives:</b> Ulcerative colitis is an incurable inflammatory bowel disease that increases the risk of colorectal cancer (CRC). 5-Fluorouracil (5-FU) is the predominant chemotherapy for CRC patients; however, undesirable side-effects, including mucositis, are common. This study utilised 5-FU-treatment in a model of colitis-associated CRC to develop a pre-clinical setting of intestinal mucositis coincident with manifestation of CRC.</p> <p><b>Materials/methods:</b> On day 0, female C57BL/6 mice (<i>n</i> = 10/group); (1) saline control, (2) AOM/DSS control, or (3) AOM/DSS + 5-FU were injected with saline or AOM (i.p; 7.4 mg/kg). Groups 2 and 3 underwent cycles of seven days 2%w/v DSS followed by 14 days plain water. After three cycles, 5-FU was administered weekly (i.p; 75 mg/kg) to group 3 for five weeks. Clinical indicators were measured daily and colonoscopy performed at four time-points. Mice were euthanized at 13 weeks (day 91). Intestinal sections were collected for histological and biochemical analyses. <i>p</i> < .05 was considered significant.</p> <p><b>Results:</b> AOM/DSS resulted in bodyweight loss, increased disease activity index, colitis-severity and tumour number compared to saline controls (<i>p</i> < .05). 5-FU-treatment in AOM/DSS mice decreased bodyweight and disease activity index at selected time-points compared to AOM/DSS controls (<i>p</i> < .05). 5-FU did not impact colitis-severity or overall tumour burden; although, resulted in fewer small tumours compared to AOM/DSS controls (<2mm; <i>p</i> < .05). AOM/DSS increased histological severity scores in intestinal sections (<i>p</i> < .05), however, 5-FU-treatment did not further increase histologically-assessed disease severity (<i>p</i> > .05).</p> <p><b>Conclusion:</b> Weekly 5-FU administration at a dose of 75 mg/kg was insufficient to reduce overall tumour burden or induce intestinal mucositis in the AOM/DSS mouse model.</p>