• Modeling Mechanism：

  N,N'-Dinitrosopiperazine (DNP), as a nitrosamine carcinogen, exhibits nasopharyngeal epithelial tissue-specific carcinogenic activity. Its core mechanisms are as follows: ① As a tumor initiator, it damages the DNA of nasopharyngeal epithelial cells after entering the body, inducing gene mutations and initiating the carcinogenesis process; ② It requires synergistic action with tumor promoters (such as Daphne odora extract, WI). WI can activate early EB virus antigens, enhance lymphocyte transformation, create a pro-cancer microenvironment, and accelerate the pathological progression of the nasopharyngeal mucosa from hyperplasia → squamous metaplasia → dysplasia → carcinoma; ③ Low-dose DNP alone (sub-carcinogenic dose) has no tumorigenic ability and requires promoters to break through the carcinogenesis threshold, ultimately forming carcinoma in situ or early invasive carcinoma, mimicking the multifactorial pathogenic characteristics of human nasopharyngeal carcinoma.

• Related Products：

  N,N'-Dinitrosopiperazine (T81720)

• Modeling Method：

  Experimental Subject：

  Rats, Hybrid rats, Equal numbers of males and females, 2 months old

  Dosage and Administration Route：

  ① Two-stage modelling:
  - Induction phase: N,N'-Dinitrosopiperazine (DNP), 9 mg/ml solution (containing a small amount of Tween 80 as a solubilising agent), 1 ml per animal, subcutaneous injection, single administration;
  - Promotion phase: 10 days after induction, administration of Wikstroemia indica extract (WI) – 10 mg/ml ethanol solution – 0.1 ml per animal – nasopharyngeal instillation – twice weekly for 7 weeks;
  ② Control treatment:
  - N,N'-Dinitrosopiperazine (DNP) monotherapy group: Subcutaneous injection of 1 ml N,N'-Dinitrosopiperazine (DNP) solution only, without WI intervention;
  - WI monotherapy group: 0.1 ml WI solution administered via nasopharyngeal instillation twice weekly for 7 weeks;

  Dosing Frequency and Duration Model：

  Single dose

• Validation：

  1. Tumor Characteristics: - Incidence: Only the DNP+WI combination group developed tumors, with 26.1% (6/23) of rats developing nasopharyngeal carcinoma, including 2 cases of carcinoma in situ and 4 cases of early invasive carcinoma (3 cases of poorly differentiated squamous cell carcinoma and 1 case of columnar cell carcinoma); - Pathological Morphology: HE staining showed that tumor cells grew in a papillary, gyral, or mushroom-like pattern, partially obstructing the nasopharyngeal cavity. Invasive carcinoma broke through the basement membrane and invaded the stroma, and some were accompanied by mucus secretion (light blue staining); 2. Precancerous Lesions: - The incidence of squamous metaplasia of the nasopharyngeal mucosa in the combination group was 82.6% (19/23), and the incidence of papillary hyperplasia was 78.3% (18/23), which was significantly higher than that in the single-drug group (incidence ≤50%); 3. Negative Control: No nasopharyngeal carcinoma occurred in the DNP and WI single-drug groups. Only the WI single-drug group showed 1 case of papilloma and 1 case of dysplasia, verifying the specificity of the model.

*Precautions： Animals were euthanized 180 days after modeling, and the nasopharyngeal tissue was completely dissected.

*References：Tang WP,et,al. Wikstroemia indica promotes development of nasopharyngeal carcinoma in rats initiated by dinitrosopiperazine. J Cancer Res Clin Oncol. 1988;114(4):429-31.