7,12-Dimethylbenz[a]anthracene (DMBA) is a polycyclic aromatic hydrocarbon (PAH) that has been found in tobacco smoke and diesel exhaust and has carcinogenic activity.^1,2It undergoes metabolic activation by numerous enzymes, including the cytochrome P450 (CYP450) isoform CYP1B1, as well as microsomal epoxide hydrolase (mEH), producing a variety of reactive metabolites that form DNA adductsin vivo, and it has been commonly used to induce tumor formation in various rodent models.^2,3,1DMBA increases proliferation and migration of, and induces epithelial-to-mesenchymal transition (EMT) in, MCF-10A breast cancer cells when used at a concentration of 5 µM.⁴It also has immunosuppressant activity, inhibiting proliferation of isolated mouse splenic B- and T cells stimulatedex vivowith LPS or concanavalin A , respectively, when administered at doses of 50 and 100 mg/kg.⁵Intragastric administration of DMBA (20 mg/animal) induces formation of mammary gland tumors in rats.⁶DMBA (50 µg/animal), in combination with phorbol 12-myristate 13-acetate , initiates papilloma formation in a rat two-stage model of skin carcinogenesis.⁷

1.Rengarajan, T., Rajendran, P., Nandakumar, N., et al.Exposure to polycyclic aromatic hydrocarbons with special focus on cancerAsian Pac. J. Trop. Biomed.5(3)182-189(2015) 2.Csiszar, A., Balasubramanian, B., Tarantini, S., et al.Chemically induced carcinogenesis in rodent models of aging: Assessing organismal resilience to genotoxic stressors in geroscience researchGeroscience41(2)209-227(2019) 3.Huberman, E., Chou, M.W., and Yang, S.K.Identification of 7,12-dimethylbenz[a]anthracene metabolites that lead to mutagenesis in mammalian cellsProc. Natl. Acad. Sci. U.S.A.76(2)862-866(1979) 4.Kwon, Y.-J., Ye, D.-J., Baek, H.-S., et al.7,12-Dimethylbenz[α]anthracene increases cell proliferation and invasion through induction of Wnt/β-catenin signaling and EMT processEnviron. Toxicol.33(7)729-742(2018) 5.Gao, J., Lauer, F.T., Dunaway, S., et al.Cytochrome P450 1B1 is required for 7,12-dimethylbenz(a)-anthracene (DMBA) induced spleen cell immunotoxicityToxicol. Sci.86(1)68-74(2005) 6.Barros, A.C.S.D., Muranaka, E.N.K., Mori, L.J., et al.Induction of experimental mammary carcinogenesis in rats with 7,12-dimethylbenz(a)anthraceneRev. Hosp. Clin. Fac. Med. Sao Paulo59(5)257-261(2005) 7.VÄhÄtupa, M., Pemmari, T., Junttila, I., et al.Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)J. Vis. Exp.154(2019)