DMBA can be used to create chemically induced skin carcinogenesis, breast cancer, and other cancer models in animal models of disease.

Absorption, Distribution and Excretion
Animal studies have shown that 7,12-dimethylbenzanthracene (7,12-DMBA) is readily absorbed from the intestine and primarily distributed in body fat and adipose tissue (e.g., mammary glands). The distribution of radioactivity in rats after administration of the labeled compound via gastric tube was investigated. The primary route of excretion is via bile into feces. The radioactivity has a longer retention time in body fat, ovaries, and adrenal glands. Rat rats were orally administered 7,12-DMBA at a dose of 20 mg/kg, which dissolves in the lipid fraction of chylomicrons in the lymph. 48 hours after oral administration, 90% of the drug was excreted by the mice. Pretreatment of mice with 3-methylcholanthrene slightly increased the initial elimination rate of 7,12-dimethylbenzanthracene (DMBA), but after 48 hours, the residual amount of 7,12-DMBA was the same as in unpretreated mice. The levels of ethyl acetate-extractable polar and water-soluble metabolites in the urine and feces of pretreated mice were higher than in unpretreated mice. Two hours after intraperitoneal injection, 7,12-dimethylbenzanthracene (DMBA) was present throughout the body of Amazonian Molly fish, except in the brain and ovaries. DMBA deposition was enhanced in four sites: atrial and peritoneal macrophages, liver, and exocrine pancreas. DMBA was taken up by reticuloendothelial macrophages within 78 hours post-injection, and then disappeared. The accumulation and disappearance of the radiolabeled material observed in liver and pancreatic cells likely represent the metabolic pattern of this compound. DMBA almost completely disappeared 400 hours post-injection. The marker accumulated in ameloblasts, which secrete enamel for teeth. No preferential metabolism of DMBA was observed in the spleen. Metabolism/Metabolites Due to the high incidence of pancreatic cancer in the United States and its association with environmental exposure, we conducted experiments to measure the metabolism of the carcinogen 7,12-dimethylbenzanthracene in the pancreas of male Long-Evans rats. This study investigated the in vitro metabolism of this carcinogen and found that the production of aqueous products in the pancreas was similar to that in the liver. However, pretreatment with phenobarbital or 3-methylcholanthrene did not induce enhanced pancreatic metabolic capacity. High-performance liquid chromatography (HPLC) analysis of in vitro pancreatic metabolites showed that the content of 5,6-epoxy-7-hydroxymethyl-12-methylbenzanthracene was relatively higher in the pancreas than in the liver, while the content of 7-hydroxymethyl-12-methylbenzanthracene and 7-methyl-12-hydroxymethylbenzanthracene was relatively lower in the pancreas than in the liver. Carcinogen levels in the pancreas, liver, bile, and blood were measured at 2, 5, 10, 16, 22, and 36 hours after injection. Homogeneous 3α-hydroxysteroid dihydrogen diol dehydrogenase in rat hepatocyte cytoplasm catalyzes the NADP-dependent oxidation of various polycyclic aromatic hydrocarbon trans-dihydrogen diols and participates in their detoxification process. This study investigated the effects of methyl on the enzymatic oxidation rate and stereochemical process of benzo[a]anthracene (BA) trans-dihydrogen diol. The purified dehydrogenases completely consumed the racemic trans-3,4-dihydrodiol of benzoic acid (BA) and 7-methylbenzanthracene (7-MBA), indicating that both stereoisomers were substrates. However, only 50% of the (+/-)-trans-3,4-dihydrodiol of 12-methylbenzanthracene (12-MBA) and 7,12-dimethylbenzanthracene (DMBA) was oxidized, suggesting that only one stereoisomer was utilized in each case. At low substrate concentrations, the enzymatic oxidation of trans-3,4-dihydrodiol of BA, 12-MBA, and DMBA followed simple first-order kinetics. In contrast, the oxidation of 3,4-dihydrodiol of 7-MBA followed higher-order kinetics, due to the different oxidation rates of each stereoisomer. Rate constant estimates for each reaction showed that the non-bay methyl group at position 7 promoted the oxidation rate more than the bay methyl group at position 12 (10-fold and 4-fold, respectively). The oxidation rate of 3,4-dihydrodiols of DMBA containing both non-bay and bay methyl groups is more than 30 times faster than that of the unmethylated parent hydrocarbon. The absolute stereochemical configuration of the preferentially oxidized dihydrodiol was determined by circular dichroism spectroscopy. The stereoisomers of oxidized 3,4-dihydrodiols of DMBA and 12-MBA have a 3S,4S configuration. A significant negative Cotton effect was observed in the circular dichroism spectroscopy of 7-MBA 3,4-dihydrodiol, appearing at the end of the rapid oxidation phase of this racemic substrate, indicating a stereochemical preference of the dehydrogenase for the 3S,4S enantiomer. These results suggest that methylation at the C-7 position of BA significantly enhances the oxidation of 3S,4S-dihydrodiols, while the bay methyl group at the C-12 position completely blocks the oxidation of the 3R,4R-steriomer. The rapid, stereoselective oxidation of methylated trans-dihydrodiols of polycyclic aromatic hydrocarbons via this pathway in vivo may significantly affect their carcinogenicity. Early studies have shown that benzo[a]anthracene (BA), 7-methylbenzo[a]anthracene (7-MBA), and 12-methylbenzo[a]anthracene (12-MBA) undergo bioalkylation substitution at the meta-anthracene group or L-block to biosynthesize the potent carcinogen 7,12-dimethylbenzo[a]anthracene (7,12-DMBA). These results support the hypothesis that for most (if not all) unsubstituted polycyclic aromatic hydrocarbon carcinogens, the introduction of an alkyl group at the meta-anthracene ring or L-block is a chemical or biochemical requirement for their potent carcinogenic activity. This paper reports that the L-block methyl derivatives 7-MBA, 12-MBA, and 7,12-DMBA can be oxidized to hydroxymethyl derivatives in rat liver cytosol without significant oxidation at the ring position. In rats, guinea pigs, pigs, and hamsters, 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenzanthracene, 7-hydroxymethyl-12-methylbenzanthracene, and 12-hydroxymethyl-7-methylbenzanthracene were generated, respectively. /Excerpt from Table/
For more complete metabolite/metabolite data on 7,12-dimethylbenzanthracene (21 metabolites in total), please visit the HSDB record page.
The known metabolites of 7,12-dimethylbenzo[a]anthracene include: benzo[a]anthracene-3,4-diol, 7,12-dimethyl-, 7,12-dimethylbenzo[a]anthracene-5,6-diol, benzo[a]anthracene-8,9-diol, 7,12-dimethyl-, 12-hydroxymethyl-7-methylbenzo[a]anthracene, 7-hydroxymethyl-12-methylbenzo[a]anthracene and benzo[a]anthracene-2-ol, 7,12-dimethyl-.

Toxicity Summary
Identification and Uses: 7,12-Dimethylbenzanthracene (DMBA) is a solid. It is primarily used as an investigational chemical in laboratory medicine. Human Exposure and Toxicity: 7,12-DMBA is one of the most potent synthetic carcinogens. In humans, skin contact may induce carcinogenic effects. DMBA showed low mutagenicity in human cell cultures after metabolic activation; however, almost no effect was observed in unactivated cultures. Animal Studies: Feeding 50-day-old female rats with 112 or 133 mg/kg body weight of DMBA resulted in pancytopenia within weeks, accompanied by severe suppression of hematopoietic and lymphoid progenitor cells. Weekly intravenous injection of DMBA caused dermal melanoma and tumors in the forestomach, intestines, ovaries, subcutaneous tissue, and lymphoreticular tissue in Syrian hamsters. A single intraperitoneal injection of 80 mg/kg DMBA (dissolved in corn oil) destroyed primordial oocytes in mouse ovaries. DMBA significantly enhanced toxicity to avian embryos. In rodent cell assays, inactivated DMBA showed weak mutagenicity, while activated DMBA showed moderate mutagenicity. It also caused sister chromatid exchange and chromosomal aberrations. The mammalian cell transformation assay for DMBA was weakly positive after metabolic activation. Ecotoxicity studies: At least 145 6- to 11-day-old king spectacles (Poecilia reticulata) were exposed to DMBA for 6 hours weekly for 4 weeks. Guppies exposed to moderate to high concentrations of DMBA developed liver tumors. In addition to liver tumors, several other types of lesions were observed in guppies exposed to DMBA.

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Interaction
Because some epidemiological studies and rat induction/promotion studies have shown that the incidence of breast cancer may increase with increasing magnetic field exposure, this study investigated the promoting effect of 50 Hz and 60 Hz magnetic fields on breast tumors induced by injection of 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley rats in a 13-week and 26-week systemic exposure experiment. In an initiation/promotion study, female Sprague-Dawley rats were injected with 5 mg/rat of DMBA weekly for 4 weeks starting at 50 days of age and exposed to a 50 Hz magnetic field of 1 G or 5 G intensity, or a 60 Hz magnetic field of 1 G intensity for 13 weeks. The results showed no evidence that the magnetic field promoted the occurrence of breast tumors. The incidence and number of breast cancers in all DMBA groups limited the ability of this assay to detect the promoting effect of the magnetic field. In another initiation/promotion study, female Sprague-Dawley rats, starting at 50 days of age, received weekly injections of 2 mg/rat of DMBA for 4 weeks and were exposed to a 50 Hz magnetic field of 1 G or 5 G intensity for 13 weeks. Results showed no evidence that the magnetic field promoted breast tumor development. In another initiation/promotion study, 50-day-old female Sprague-Dawley rats, after a single injection of 10 mg DMBA, were exposed to a 50 Hz magnetic field of 1 G or 5 G intensity, or a 1 G 60 Hz magnetic field for 26 weeks. Results showed no evidence that the magnetic field promoted breast tumor development. The purpose of this study was to investigate the effects of ultraviolet B (UVR-B) and dimethylbenzanthracene (DMBA) on tumorigenesis. Forty Wistar rats were randomly divided into four groups (n=10 per group): Group A received UVR-B irradiation, Group B received topical DMBA application, Group C received UVR-B + DMBA irradiation, and Group D served as the control group, with observation for ten weeks. At week 10, skin biopsies and histopathological examinations were performed on all rats. Mean epidermal thickness was calculated and statistically analyzed. Compared to group A, the visible lesions in group B were more inflammatory. The proportion of neoplastic lesions was higher in group C than in other groups (p<0.01). Histological examination showed that epidermal thickness was significantly increased in all groups compared to the control group, but the epidermal thickness was greatest in group C (p<0.01). Exposure to UVB radiation increases the risk of skin lesions, which may develop into cancer. Combination with hydrocarbons such as dimethylbenzanthracene increases the risk of malignant tumors. …Cruciferous vegetables contain high levels of glucosinolates, and their metabolites are thought to enhance detoxification. Spanish black radish (SBR) contains four times more glucosinolates than other cruciferous vegetables. This study investigated whether feeding mice a diet containing 20% SBR for two weeks enhanced the metabolism of 7,12-dimethylbenzanthracene (DMBA) and inhibited DMBA-mediated myelotoxicity. The results showed that the expression of phase I and phase II detoxification enzymes in mice fed with SBR diets was significantly higher than that in the control group. Six hours after DMBA administration, the concentration of DMBA in the blood of mice fed with SBR diets was significantly lower than that in mice fed with control diets. The reduction of bone marrow cells by DMBA in control mice was significantly greater than that in mice fed with SBR diets. Colony formation assays showed that mice fed with SBR diets: 1) had less reduction in lymphocyte colony-forming unit-preB cells (CFU-preB); 2) had greater recovery of CFU-preB cells after 168 hours; and 3) had less reduction in CFU-GM cells after 6 hours. Therefore, mice fed a diet containing 20% SBR for 2 weeks had higher levels of detoxification enzyme expression, faster DMBA metabolism, and reduced DMBA-induced bone marrow toxicity. Overall, these results support the hypothesis that glucosinolates in SBR have a protective effect against acute toxicity. Human lymphocytes were exposed to a binary mixture of mutagens B[a]P, DMBA, Trp-P-1, and MX for 1 hour, with or without S9. Cell viability was assessed using trypan blue staining, and genotoxicity was assessed using a comet assay. All hydrocarbons interacted with furanones. The most toxic interactions among hydrocarbons were observed with or without S9. In the absence of S9, synergistic effects were observed between B[a]P and Trp-P-1, and between DMBA and Trp-P-1, accompanied by metabolic activity. Antagonism was observed only between Trp-P-1 and DMBA without S9; with S9, antagonism was observed only between Trp-P-1 and MX and MX and DMBA. A dose-dependent increase in tail length was observed. Half of the cultures showed genotoxic damage and increased cell damage. ...
For more complete data on interactions of 7,12-dimethylbenzo[a]anthracene (27 in total), please visit the HSDB record page.

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Non-human toxicity values
Intratracheal LD50 in mice: 22,500 μg/kg
Intraperitoneal LD50 in mice: 54 mg/kg
Oral LD50 in mice: 340 mg/kg
Intravenous LD50 in rats: 54 mg/kg
Oral LD50 in rats: 327 mg/kg

[1]. Csiszar A, Balasubramanian P, Tarantini S, Yabluchanskiy A, Zhang XA, Springo Z, Benbrook D, Sonntag WE, Ungvari Z. Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research. Geroscience. 2019 Apr;41(2):209-227.

According to the U.S. Environmental Protection Agency (EPA), 7,12-dimethylbenzo[a]anthracene is carcinogenic. 7,12-Dimethylbenzo[a]anthracene is a yellow to yellowish-green crystal or yellow solid, odorless, with a maximum fluorescence wavelength of 440 nm, emitting blue-violet fluorescence under ultraviolet light. (NTP, 1992) 7,12-Dimethyltetraphenyl is a tetraphenylene compound with methyl substituents at the 7 and 12 positions. It is a potent carcinogen found in tobacco smoke. It is a carcinogen belonging to the tetraphenyl group of compounds and is also an ortho-fused polycyclic aromatic hydrocarbon. A potent carcinogen found in tobacco smoke—polycyclic aromatic hydrocarbons. See also: benzo[a]anthracene, 9,10-dimethyl- (note moved to).

C20H16

256.34

256.125

57-97-6

6001

Plates, leaflets from acetone-alcohol, faint greenish-yellow tinge
Pale yellow plates from alcohol, acetic acid

1.1±0.1 g/cm3

463.5±15.0 °C at 760 mmHg

122-123 °C(lit.)

227.3±14.5 °C

0.0±0.5 mmHg at 25°C

1.729

6.83

0

0

0

20

346

0

C12C3=C([H])C([H])=C([H])C([H])=C3C([H])=C([H])C1=C(C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1C=2C([H])([H])[H]

ARSRBNBHOADGJU-UHFFFAOYSA-N

InChI=1S/C20H16/c1-13-16-8-5-6-9-17(16)14(2)20-18(13)12-11-15-7-3-4-10-19(15)20/h3-12H,1-2H3

7,12-dimethylbenzo[a]anthracene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 25 mg/mL (97.53 mM)
Acetone: 25 mg/mL (97.53 mM)
Ethanol: 3.33 mg/mL (12.99 mM)

Solubility in Formulation 1: 2.5 mg/mL (9.75 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2 mg/mL (7.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)