• Modeling Mechanism：

  N-Nitrosomorpholine (NNM), a liver-specific chemical carcinogen, is introduced into mice through drinking water. It is activated by liver metabolic enzymes (such as cytochrome P450), producing alkylating intermediates that cause DNA damage in hepatocytes (such as base alkylation and chain breaks), initiating the "initiation-promotion" process of hepatocellular carcinoma. Continued exposure can induce abnormal hepatocyte proliferation, forming precancerous liver lesions (including G6Pase-negative and G6Pase-positive lesions) with altered glucose-6-phosphatase (G6Pase) activity. This provides a target for subsequent tumor promoters (such as TCBs), mimicking the pathological basis of early-stage human liver tumors.

• Related Products：

  N-Nitrosomorpholine (T40684)

• Modeling Method：

  Experimental Subject：

  Mice, B6C3F1, Male

  Dosage and Administration Route：

  ① Core modelling (initiation phase):
  - Carcinogen exposure: N-nitrosomorpholine, 160 mg/L, dissolved in drinking water, ad libitum consumption;
  - Interval period: Following cessation of N-nitrosomorpholine administration, standard drinking water provided for 22 weeks (allowing natural development of precancerous lesions);
  - Promoter phase (optional): 3,4,3′,4′-tetrachlorobiphenyl (TCB), 50 mg/kg, intraperitoneal injection or oral gavage, once every 3 days for 5 doses, commencing after the interval period;
  ② Control treatment: Control group administered ordinary drinking water without N-nitrosomorpholine; all other housing and treatment conditions identical;

  Dosing Frequency and Duration Model：

  Free access for 7 weeks

• Validation：

  1. Pathological Indicators: - Liver Lesion Count: 29 weeks after modeling, G6Pase-negative and positive precancerous lesions were visible in the liver, with the total number of lesions per liver significantly higher than that in the control group; after combined TCB treatment, although the number of lesions decreased to 32%-57% of the control group, the proportion of large lesions (>0.5 mm²) increased, and the average volume increased; - Tissue Damage: HE staining showed disordered hepatocyte arrangement and abnormal cytoplasm; long-term treatment showed persistent liver inflammation and cell necrosis; 2. Enzymatic Indicators: - Serum Transaminases: The level of aspartate aminotransferase (AST) was significantly elevated, indicating persistent liver damage; 3. Histochemical Indicators: - G6Pase Activity Detection: Histochemical staining showed abnormal G6Pase activity (negative or positive) in the lesion area, which is a characteristic marker of precancerous lesions.

*Precautions：

*References：Ren L,et,al. Vasculoprotective effects of rosiglitazone through modulating renin-angiotensin system in vivo and vitro. Cardiovasc Diabetol. 2011 Jan 26;10:10.