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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.1,2 It 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 adducts in vivo, and it has been commonly used to induce tumor formation in various rodent models.2,3,1 DMBA 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.4 It also has immunosuppressant activity, inhibiting proliferation of isolated mouse splenic B- and T cells stimulated ex vivo with LPS or concanavalin A , respectively, when administered at doses of 50 and 100 mg/kg.5 Intragastric administration of DMBA (20 mg/animal) induces formation of mammary gland tumors in rats.6 DMBA (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.Vhtupa, 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)

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