• Modeling Mechanism：

  Nitrofurazone, a nitro-containing furan compound, induces breast tumors through the following mechanisms: ① The nitro group is activated by nitro reductase metabolism in vivo, generating a genotoxic active intermediate that binds to breast epithelial cell DNA, causing base damage and gene mutations; ② In vitro experiments have confirmed that it can induce Salmonella gene mutations, sister chromatid exchange in Chinese hamster ovary cells, and chromosomal aberrations. In vivo, it initiates malignant transformation of breast epithelial cells by interfering with the balance of cell proliferation and repair; ③ The nitro group in the molecular structure is a key carcinogenic group. Nitro-free structural analogs cannot induce breast tumors, and ultimately mainly form breast fibroadenomas, some of which can progress to adenocarcinoma.

• Related Products：

  Nitrofurazone (T0897)

• Modeling Method：

  Experimental Subject：

  Rats, F344/N rats, Female, 6–7 weeks old (pre-pubertal)

  Dosage and Administration Route：

  ① Core modelling: Nitrofurazone, 310 ppm or 620 ppm, mixed into standard diet, ad libitum access;
  ② Actual intake: Low dose (310 ppm) approximately 12 mg/kg/day, high dose (620 ppm) approximately 26 mg/kg/day;
  ③ Control treatment: Control group received basal diet without Nitrofurazone; all other housing conditions identical;

  Dosing Frequency and Duration Model：

  Ad libitum feeding, Continuous for 103 weeks (approximately 2 years)

• Validation：

  1. Tumor Incidence: - Breast fibroadenoma: The incidence rate was 16% (8/49) in the control group, 72% (36/50) in the low-dose group, and 72% (36/50) in the high-dose group, showing a highly significant difference compared to the control group (p<0.001); - Breast adenocarcinoma: The incidence rate was 2% (1/49) in the control group and 4% (2/50) in the high-dose group, showing a slight increasing trend; 2. Pathological Indicators: - HE staining showed that breast fibroadenoma was composed of epithelial tissue and fibrous connective tissue. Small tumors were mainly composed of epithelial components, while large tumors were dominated by fibrous connective tissue, which could compress or replace epithelial structures; adenocarcinoma showed abnormal proliferation, morphological atypia, and invasive growth of epithelial cells; 3. Genetic Toxicity Verification: - Positive in vitro Salmonella TA98 and TA100 gene mutation tests, and increased sister chromatid exchange and chromosomal aberration rates in Chinese hamster ovary cells, confirming its genotoxic effects.

*Precautions： At the end of the experiment, the breast tissue (including all lobes) was completely dissected after euthanasia. Tumor nodules and adjacent tissues were separated, and some were fixed in 10% neutral formalin (for pathological staining and immunohistochemistry), while others were flash-frozen in liquid nitrogen (for molecular mechanism detection).

*References：National Toxicology Program. NTP Toxicology and Carcinogenesis Studies of Nitrofurazone (CAS No. 59-87-0) in F344/N Rats and B6C3F1 Mice (Feed Studies). Natl Toxicol Program Tech Rep Ser. 1988 Jun;337:1-183.