MODELO DE CÂNCER COLORRETAL QUIMICAMENTE INDUZIDO EM CAMUNDONGOS HAIRLESS ASSOCIADO A COLITE

Abstract

Objective: This study aimed to develop a model of colorectal cancer in hairless mice induced with azoxymethane (AOM) associated with colitis. Methods: The results were obtained through an experimental study in a murine model. The study was developed at the Faculty of Medicine of the Federal University of Mato Grosso Do Sul, in the city of Campo Grande, MS. In this study, 140 animals were distributed in 5 groups of 28 animals: G1: control; G2: 2 doses of AOM; G3: 1 dose of AOM and 3 cycles of dextran sulfate of sodium (DSS) ad libitum; G4: 2 doses of AOM and 3 cycles of DSS ad libitum; and G5: 3 cycles of DSS ad libitum. The mice were induced to develop colorectal cancer (CCR) with a total dose of 20 mg/Kg of azoxymethane, divided into two weeks of 10 mg/kg per week, with the first dose in the third week and the second dose in the fourth week. Stress and anxiety in post-DSS animals and before euthanasia were evaluated in all groups. For colitis induction, 3 cycles of DSS were administered for 5 days, interspersed with 2 weeks of tap water ad libitum. In the fifth, tenth, fifteenth, and twentieth weeks of the experiment, seven mice from each group were submitted to a euthanasia procedure, their colons were removed for macroscopic and microscopic analysis, and microscopy slides were made to allow the histological classification of lesions found, aiming at a comparison between the findings in the experimental groups. Results: Of the total number of polyps, a significant gain was observed at the 10th, 15th, and 20th weeks on average. By histopathological analysis, from the 10th week on, the animals induced with AOM/DSS developed pre-neoplastic lesions, with differences between the other groups when compared to the control group. From aberrant crypt foci to high-grade dysplasia, these were visualized in the induced groups. Regarding stress and anxiety, an increase in the time spent in the peripheral zone of the open field test was found, indicating an increase in the mice’s stress and anxiety. Conclusion: The groups that received AOM and DSS were the ones that developed the most polyps and pre-neoplastic lesions, indicating that colitis associated with tumor induction is an effective method of developing a rapid model for CRC studies.