• Modeling Mechanism：

  Terephthalic acid (TPA), a classic skin tumor promoter, induces skin cancer through the following core mechanisms: ① Directly activates epidermal keratinocyte proliferation signals, disrupting the balance between epidermal proliferation and differentiation, promoting the expansion of abnormal cell clones, and providing a basis for carcinogenesis; ② Enhances skin barrier permeability, promoting the transdermal absorption and DNA damage effects of initiating carcinogens (such as DMBA); ③ Species/genetic background dependence: low doses (10 ng) can induce proliferation of porcine skin, porcine skin transplanted into nude mice, and nude mouse heterozygous (nu/+) skin, while nude mouse homozygous (nu/nu) skin requires high doses (100 ng) to respond, and its pro-cancer activity is related to recessive genetic traits; ④ Synergistic effect with the inflammatory microenvironment: high doses or combined stimulation induce the release of inflammatory factors, further accelerating the carcinogenesis process, ultimately leading to skin papilloma or squamous cell carcinoma.

• Related Products：

  Terephthalic acid (T8031)

• Modeling Method：

  Experimental Subject：

  Mice, Nude mice (homozygous nu/nu, heterozygous nu/+), pig skin-transplanted nude mouse model, 2–3 months old (acclimatised post-transplantation), pig skin donor being healthy domestic pig

  Dosage and Administration Route：

  ① Two-stage modelling:
  - Initiation phase: Topical application of carcinogenic initiator (e.g., 7,12-dimethylbenzo[a]anthracene, DMBA), 50 μg/site, dissolved in acetone, single application, followed by initiation of promotion phase after 2 weeks;
  - Promotion phase: Topical application of Terephthalic acid at low dose (10 ng/site for pig skin/homozygous nude mice) or high dose (100 ng/site for homozygous nude mice), dissolved in 50% dimethyl sulfoxide (DMSO)+50% acetone (D/A=1:1);
  ② Single-dose proliferation validation (pre-experimental modelling):
  - Topical application of Terephthalic acid, 10–100 ng/site, single application, with epidermal proliferation activity assessed after 18 hours;
  ③ Control treatment:
  - Blank control: application of equal volume solvent (D/A or acetone);
  - Transplant control: Pig skin grafted onto nude mice vs. autologous skin grafts administered concurrently;

  Dosing Frequency and Duration Model：

  Promotion phase: 1–2 times weekly for 16–20 weeks; Single-dose proliferation validation: single dose

• Validation：

  1. Proliferation Indicators: - Labeling Index (LI): The LI of epidermal basal cells was significantly increased in the TPA treatment group (ΔLI was significant in the 10 ng TPA group of porcine skin, and the LI of the homozygous nude mouse 100 ng TPA group was more than 1.8 times that of the control group, p<0.005); - Epidermal Morphology: HE staining showed an increase in epidermal thickness of more than 30%, an extension of the proliferating cell layer, and disordered cell arrangement; 2. Tumor Characteristics: - Incidence: After two-stage modeling, the tumor incidence rate in heterozygous nude mice and porcine skin transplantation models was ≥60%, and in homozygous nude mice it reached 66% (32 weeks), mainly papillomas, with some progressing to squamous cell carcinoma; - Pathological Verification: HE staining showed tumor cell atypia, hyperkeratosis, and invasive features, and immunohistochemistry showed a significant increase in the positive rate of proliferation markers (such as Ki-67); 3. Species/Genetic Response: - Low-dose (10 ng) TPA It only induced proliferation of porcine skin, porcine skin grafts, and heterozygous nude mouse skin; homozygous nude mice showed no response; and high doses (100 ng) could exceed the threshold.

*Precautions：

*References：Krueger GG,et,al. Epidermal proliferation of nude mouse skin, pig skin, and pig skin grafts. Failure of nude mouse skin to respond to the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate. J Exp Med. 1980 Nov 1;152(5):1329-39.