• Modeling Mechanism：

  Dextran sulfate sodium salt (DSS) induces chronic ulcerative colitis by disrupting the colonic mucosal barrier, causing intestinal flora imbalance, and inducing macrophage/lymphocyte dysfunction. This leads to repeated necrosis and regeneration of the colonic mucosa, forming a "damage-repair" cycle, promoting abnormal proliferation and regenerative dysplasia of epithelial cells, and providing a "pro-cancer microenvironment" for tumorigenesis. Pre-administration of AOM (a procarcinogen) activates it through metabolism to generate alkylating agents, which alkylate the DNA of colonic mucosal cells, initiating tumorigenesis.

• Related Products：

  Dextran sulfate sodium salt (MW 36,000 - 50,000) (T13647L)

• Modeling Method：

  Experimental Subject：

  Mice, CBA/J mice, Female, 6 weeks of age

  Dosage and Administration Route：

  ① Core Modelling (Synergistic Protocol):
  - Induction phase: Intraperitoneal injection of AOM, 7.4 mg/kg, single dose at 7 weeks of age;
  - Promotion phase: Following AOM administration, undergo three cycles of Dextran sulfate sodium salt intervention (each cycle: 7 days of free access to 3% Dextran sulfate sodium salt solution+14 days of free access to distilled water);
  ② Control treatment:
  - Dextran sulfate sodium salt monotherapy group: intraperitoneal injection of saline+3 cycles of Dextran sulfate sodium salt intervention;
  - Blank control: Intraperitoneal injection of physiological saline+distilled water throughout the entire period

  Dosing Frequency and Duration Model：

  Promotion phase: Each cycle: 7 days of free access to 3% Dextran sulfate sodium salt solution+14 days of free access to distilled water)

• Validation：

  1. Tumor Characteristics: - Incidence: Colorectal tumors appeared only in the AOM+DSS combined group, with an average of 10.5 tumors per mouse, mainly distributed in the left colon and transverse colon (the most severely affected areas of colitis); - Pathological Type: 95.9% were high-grade dysplasia, and 4.1% were submucosal invasive adenocarcinomas. HE staining showed significant tumor cell structure/cellular atypia, with some accompanied by lymphoid follicle formation; 2. Inflammatory Markers: - Colitis Pathological Score: The left colon score in the combined group reached 3.2±0.4 (control group ≤0.3), showing mucosal ulceration, gland loss, and inflammatory cell infiltration; - Fecal Occult Blood: The positive rate of fecal occult blood during DSS intervention was ≥89%, and it turned negative in distilled water during the recovery period; - Colon Morphology: The colorectal length in the combined group was shortened to 103.5±4.7 mm (control group ≥114 mm, p<0.001); 3. Proliferative Markers: - Immunohistochemistry of bromodeoxyuridine (BrdU) showed that proliferating cells in tumor tissue were distributed throughout the entire thickness (proliferating areas in non-tumor mucosa were limited to the basal layer); - Enzyme activity: The activities of thymidine synthase (TS) and thymidine kinase (TK) in tumor tissue were significantly increased (TS activity was more than 2 times higher than that in the control group, p<0.01).

*Precautions： At the end of the 11th week, the surviving animals were euthanized under ether anesthesia.

*References：Okayasu I,et,al. Promotion of colorectal neoplasia in experimental murine ulcerative colitis. Gut. 1996 Jul;39(1):87-92.