• Modeling Mechanism：

  Chrysene, a polycyclic aromatic hydrocarbon (PAH) carcinogen, is oxidized in the liver by microsomal mono-oxygenases to form epoxide metabolites (such as K-region epoxide, chrysene 5,6-oxide). These reactive intermediates can bind to hepatocyte DNA to form adducts, inducing gene mutations. Simultaneously, neonatal mouse hepatocytes are in a state of rapid division and are highly sensitive to carcinogens. Furthermore, the low level of epoxide hydrolases in neonatal tissues makes it difficult to rapidly inactivate epoxides, ultimately leading to abnormal hepatocyte proliferation and the formation of liver tumors.

• Related Products：

  Chrysene (T14961)

• Modeling Method：

  Experimental Subject：Mice: Newborn Swiss mice aged 0–2 days postnatal (within the first 3 days)

  Dosage and Administration Route：① Core modelling: Chrysene, 100 μg per dose, suspended in polyethylene glycol (PEG) 400, 0.02 ml suspension injected per animal, subcutaneous injection (needle insertion at base of tail, injection site in interscapular region); ② Control treatment: Control group administered equal volume of PEG 400 subcutaneously, with identical timing and frequency to modelling protocol; ③ Housing Management: Following weaning at 21 days of age, males and females housed separately (6 per cage). Fed standard chow (Formulation 86), with free access to water. Bedding comprised a mixture of sawdust and wood shavings. Housing conditions were unmodified (standard laboratory conditions).

  Dosing Frequency and Duration Model：A total of three administrations were conducted on days 0, 1, and 2 post-birth.

• Validation：

  1. Tumor Incidence: - 70-75 weeks after modeling, the incidence of liver tumors in male mice was significantly increased. In the Chrysene-treated group (Group H), 13 out of 27 surviving male mice developed liver tumors (48.1%), of which 6 had multiple liver tumors. In the control group (Group O), 9 out of 30 male mice developed liver tumors (30%), with only 1 having multiple liver tumors. The difference was statistically significant. 2. Pathological Morphology: - All liver tumors originated from parenchymal cells. Histologically, they ranged from highly differentiated hepatocyte clusters that were difficult to distinguish from normal liver tissue to pleomorphic, invasive, and metastatic tumors. Most tumors were larger than 1 cm in diameter and were visible to the naked eye.

*Precautions：

*References：Grover PL,et,al. The carcinogenicity of polycyclic hydrocarbon epoxides in newborn mice. Br J Cancer. 1975 Feb;31(2):182-8.