• Modeling Mechanism：

  Okadaic acid ammonium salt is a non-TPA tumor promoter that does not bind to TPA receptors or activate protein kinase C (PKC). It promotes polyamine synthesis and cell proliferation by specifically inducing increased activity of ornithine decarboxylase (OrnDCase) and histidine decarboxylase (HisDCase). When combined with the carcinogen 7,12-dimethylbenzo[a]anthracene (DMBA) to initiate gene mutations, it accelerates the clonal expansion of mutant cells, ultimately inducing tumors such as skin papilloma and squamous cell carcinoma.

• Related Products：

  Okadaic acid ammonium salt (T39183)

• Modeling Method：

  Experimental Subject：

  Mouse, CD-1, Female, 8 weeks old

  Dosage and Administration Route：

  ① Initiation: 100 μg DMBA, dissolved in 0.1 mL acetone, dorsal dermal application;
  ② Promotion: 10 μg okadaic acid dissolved in 0.1 mL acetone, applied topically to dorsal skin

  Dosing Frequency and Duration Model：

  Initiation: single dose; Promotion: twice-weekly application for 30 weeks

• Validation：

  Clinical phenotype: Tumor incidence reached 93% at week 16, and the average number of tumors per mouse was 2.6 at week 30; only 6.7% (1/15 mice) of mice in the DMBA or OA alone group developed tumors; in the positive control (DMBA+teleocidin) group, all mice developed tumors at week 15, with an average of 6.8 tumors per mouse; Histological markers: 92.3% of the 39 tumors were papillomas, 5.1% were squamous cell carcinomas, and 2.6% were sarcomas, similar to the proportions of tumor types induced by TPA-type promoters; Molecular markers: Skin OrnDCase activity peaked 4 hours after OA application (1.38 nmol CO₂/mg protein/30 min), and HisDCase activity significantly increased 13 hours later (143 pmol CO₂/mg protein/hour), and OrnDCase induction could be inhibited by 13-cis-retinoic acid; Specificity verification: OA (≤100 μM) does not inhibit the specific binding of [³H] TPA to skin particle components, and does not activate in vitro PKC at ≤1.2 μM, confirming it as a non-TPA type tumor promoter.

*Precautions： All mice were euthanized after the experiment.

*References：Suganuma M,et,al. Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1768-71.