• Modeling Mechanism：

  Benzo[a]pyrene,B (a)P, as a typical polycyclic aromatic hydrocarbon carcinogen, is metabolized and activated by liver/lung tissue microsomal enzymes (such as cytochrome P450) after entering the body, generating the key intermediate 7,8-dihydrodiol, which is further converted into the ultimate carcinogen 7,8-dihydrodiol-9,10-epoxide. This active intermediate covalently binds to lung cell DNA to form an adduct, inducing gene mutations (such as damage to guanine sites), while simultaneously activating oxidative stress and inflammatory pathways, inhibiting DNA repair function, and inducing abnormal proliferation of lung epithelial cells over a long period, ultimately leading to lung cancer.

• Related Products：

  Benzo[a]pyrene (T6985)

• Modeling Method：

  Experimental Subject：

  Mice, C57BL mice, Male, 12 weeks old (adult)

  Dosage and Administration Route：

  ① Core modelling:
  - Route of administration: Intra-glandular injection;
  - Drug preparation: Benzo[a]pyrene emulsified in water-soluble KY gel to form a suspension;
  - Dose: 0.1–2.0 mg/animal, administered at 0.05 ml/animal volume;
  ② Control treatment: Control group administered equivalent volume of KY gel vehicle emulsion injection; all other housing and treatment conditions identical;
  ③ Combined modelling (optional): May be co-administered with 7,8-dihydrodiol (Benzo[a]pyrene metabolic intermediate)

  Dosing Frequency and Duration Model：

  Single dose

• Validation：

  1. Tumor Incidence: - Dose-dependent characteristics: The tumor incidence rate reached 90% in the 0.5 mg/animal group (significantly higher than 40% in the 0.1 mg/animal group and 56% in the 2.0 mg/animal group), which is the optimal modeling dose; - Tumor types: mainly local tumors at the injection site, including fibrosarcoma and rhabdomyosarcoma, with some lung metastases (needle pathological confirmation of lung tissue origin is required); 2. Pathological Indicators: - HE staining: Atypical proliferation and nested arrangement of epithelial cells are visible in lung tissue, with invasive growth of tumor cells, and some accompanied by interstitial fibrosis and inflammatory cell infiltration; - Special staining: Wiegert iron hematoxylin staining can show the characteristic myofibril structure of subtypes such as rhabdomyosarcoma; 3. Molecular Indicators: - DNA adduct detection: B(a)P-DNA covalently bound products can be detected in lung tissue DNA, which is direct evidence of carcinogenic activation; - Gene mutations: guanine site-related gene mutations (such as DNA repair genes or oncogene abnormalities) can be detected.

*Precautions：

*References：Wigley CB,et,al. Different tumours induced by benzo(a)pyrene and its 7,8-dihydrodiol injected into adult mouse salivary gland. Br J Cancer. 1978 May;37(5):657-61.