Induction of colorectal carcinogenesis in the C57BL/6J and A/J mouse strains with a reduced DSS dose in the AOM/DSS model

Abstract

Background Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and thus mouse models of CRC are of significant value to study the pathogenesis. The Azoxymethane/Dextran sulfate sodium (AOM/DSS) model is a widely used, robust initiation-promotion model for chemical induction of colitis-associated CRC in rodents. However, the dosage of chemicals, treatment regimens and outcome measures vary greatly among studies employing this model. Thus, the aim of this study was to examine an AOM/DSS model involving a reduced (1%) dose of DSS for induction of carcinogenesis in A/J and C57BL/6J (B6) mice. Results We show that colonic preneoplastic lesions can be reliably detected in A/J and B6 mice by use of a AOM/DSS model involving a single injection of 10 mg/kg AOM followed by three 7-day cycles of a low-dose (1%) DSS administration. Supporting existing evidence of A/J mice exhibiting higher susceptibility to AOM than B6 mice, our AOM/DSS-treated A/J mice developed the highest number of large colonic lesions. Clinical symptoms in both strains subjected to the AOM/DSS treatment did not persist in-between treatment cycles, demonstrating that the animals tolerated the treatment well. Conclusions Our findings suggest that a reduced dose of DSS in the AOM/DSS model can be considered in future studies of early phase colorectal carcinogenesis in the A/J and B6 mouse strains using preneoplastic lesions as an outcome measure, and that such regimen may reduce the risk of early trial terminations to accommodate human endpoints. Overall, our data emphasize the importance of devoting attention towards choice of protocol, outcome measures and mouse strain in studies of CRC in mice according to the study purpose.

Naturalizing laboratory mice by housing in a farmyard-type habitat confers protection against colorectal carcinogenesis

“…At 7 weeks of age, colonic carcinogenesis was induced in the animals by use of a previously established protocol combining Azoxymethane (AOM; Sigma-Aldrich; 10 mg/kg) and repeated DSS (MP Biomedicals; 1% w/v, dissolved in distilled H 2 O) administration. 63 Under transient gas anesthesia (isofluorane 3–4%, 200 mL/min), mice were either injected with AOM or sterile NaCl (B.Braun; 0.9%) subcutaneously into the neck skin fold. DSS (36,000–50,000 M.Wt.)…”

GTP binding protein 2 maintains the quiescence, self-renewal, and chemoresistance of mouse colorectal cancer stem cells via promoting Wnt signaling activation

“…AOM was diluted in sterile saline at a concentration of 2.5 mg/ml. The model was established according to previous reports with minor modifications [ 19 , 20 ]. Briefly, mice were injected intraperitoneally with 10 mg AOM per kg mouse weight.…”

Sirtuin 2 up‐regulation suppresses the anti‐tumour activity of exhausted natural killer cells in mesenteric lymph nodes in murine colorectal carcinoma

“…AOM was diluted in sterile saline at a concentration of 2.5 mg/mL. The model was established according to previous reports with minor modifications 22,23 . Briefly, mice were injected intraperitoneally with 10 mg AOM per kg mouse weight.…”

“…The model was established according to previous reports with minor modifications. 22,23 Briefly, mice were injected intraperitoneally with 10 mg AOM per kg mouse weight. After 6 days, mice were treated with three cycles of 2% DSS for 7 days in drinking water, followed by 2 weeks of regular drinking water (Figure S1).…”