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, 21 (4), 271-278

The Effect of Sex on the Azoxymethane/Dextran Sulfate Sodium-treated Mice Model of Colon Cancer

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The Effect of Sex on the Azoxymethane/Dextran Sulfate Sodium-treated Mice Model of Colon Cancer

Sun Min Lee et al. J Cancer Prev.

Abstract

Background: The colitis-associated cancer exhibits different characteristics according to sex in the initiation and progression of the tumors. The aim of this study was to investigate the sex-associated difference in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer model.

Methods: The AOM/DSS ICR mouse model was established to compare male with female, and then the severity of colitis-associated carcinogenesis was examined macroscopically and histologically regarding the number, size, and location of tumors. Subsequently, levels of colonic mucosal cytokine, interleukin (IL)-1β and myeloperoxidase (MPO) were assessed.

Results: At the 16th week, the tumor multiplicity and the pro-inflammatory factors differed according to sex. The total tumor number was significantly higher in male (P = 0.020) and the number of large tumors (diameter > 2 mm) was higher in male (P = 0.026). In male, the tumors located more in distal colon (P = 0.001). MPO was significantly higher in AOM/DSS-treated male mice compared to the control group (P = 0.003), whereas the corresponding female group showed no significant change (P = 0.086). Colonic IL-1β level significantly increased in AOM/DSS groups compared to control groups both in male and female (male, P = 0.014; female, P = 0.005). It was higher in male group; however, there was no statistical significance (P = 0.226).

Conclusions: In AOM/DSS murine model, colitis-associated colon tumorigenesis are induced more severely in male mice than female probably by way of inflammatory mediators such as IL-1β and MPO. The sex-related differences at the animal model of colon cancer suggest the importance of approach to disease with sex-specific medicine in human.

Keywords: Colitis; Colonic neoplasms; Disease models; Sex; animal.

Figures

Figure 1
Figure 1
Sex-associated differences in the colon adenoma and cancer induced with AOM/DSS. (A) Experimental protocol for the induction of colitis and colon cancer by AOM and DSS. (B) Representative macroscopic view of colons in each group sacrificed at week 16. (C) Representative histological images in 4th week (a) control male; AOM/DSS (b) male; (c) female. 10th week AOM/DSS (d) male; (e) female. 16th week AOM/DSS (f) male; (g) female. Occurrence of low grade adenoma in b; adenocarcinoma with focal submucosal invasion in d; high grade adenoma in e; adenocarcinoma with submucosal invasion in f; and adenocarcinoma in g (H&E; × 200 for a–c, × 100 for d and e, × 40 for f and g). Adenoma were indicated with dashed line circle; adenocarcinoma with full line circle; and submucosal invasion with arrows. M, male; F, female; AOM, azoxymethane; DSS, dextran sulfate sodium.
Figure 2
Figure 2
Tumor number according to (A) sex and (B) the colonic location. Data were expressed as mean ± SE. aP < 0.05 comparing distal and proximal; bP < 0.05 comparing male and female.
Figure 3
Figure 3
The levels of (A) myeloperoxidase (MPO) and (B) interleukin (IL)-1β in colonic mucosa measured with ELISA. Data were described as mean ± SE. aP < 0.05 comparing control and azoxymethane/dextran sulfate sodium (AOM/DSS); bP < 0.05 comparing male and female; cP < 0.05 compared to week 4; dP < 0.05 comparing week 10 and 16.

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