Experimental carcinogenesis with 7,12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates.


Introduction: DMBA is a chemical carcinogen that induces carcinomas within a few weeks of its application. We developed an experimental model of carcinogenesis induced by DMBA dissolved in 0,5% paraffin oil (DMBA-PO), verifying the inhibitory effect of the carcinogenicity of phenyl isothiocyanate (PhITC), phenethyl (PhnITC) and benzyl isothiocyanate (BITC).
Material and Methods: For this, 88 hamsters were distributed into three groups: one exposed to DMBA-PO (Group 1, n=12), three subgroups (n=12) exposed to PhITC, PhnITC, BITC and DMBA-PO (Group 2, n=36) and four control subgroups (n=10) that were not exposed to the carcinogen in which PO (paraffin oil) and isothiocyanates were applied (Group 3, n=40).
Results: The experiment had a duration of 20 weeks, at the end of which the inhibitory effect was established by comparing the lesions developed in the groups that received isothiocyanates with the group that was only treated with DMBA-PO. The carcinogenic effect of DMBA-PO is 100% (35 carcinomas) and the inhibitory effect was 0, whereas in the presence of isothiocyanates the carcinogenic effect decreases, with an inhibitory effect of 86% for BITC (5 carcinomas) and 74% for PhITC (9 carcinomas).
Conclusion: The inhibitory effect for PhnITC is 80% in relation to invasive OSCC (1 carcinoma).


[1]. Solt DB, Shklar G. Rapid induction of gamma-glutamyl transpeptidase-rich intraepithelial clones in 7,12-dimethylbenz(a)anthracene-treated hamster buccal pouch. Cancer Res. 1982;42(1):285-91. PMID: 6119154.

[2]. Solt DB, Polverini PJ, Ray S, Fei Y, Biswas DK. Early neoplastic commitment of hamster buccal pouch epithelium exposed biweekly to 7,12-dimethylbenz[a]anthracene. Carcinogenesis. 1988;9(12):2173-7. doi: 10.1093/carcin/9.12.2173. PMID: 3142694.

[3]. Nagabhushan M, Ng YK, Elias R, Polverini PJ, Solt DB. Acute inhibition of DNA synthesis in hamster buccal pouch epithelium exposed to indirect acting carcinogens. Cancer Lett. 1990;53(2-3):163-73. doi: 10.1016/0304-3835(90)90210-o. PMID: 2119880.

[4]. Salley JJ. Experimental carcinogenesis in the cheek pouch of the Syrian hamster. J Dent Res. 1954;33(2):253-62. doi: 10.1177/00220345540330021201. PMID: 13152263.

[5]. García FJG, Ortega VV, Sánchez NA, Jornet PL. Estudio comparativo de la aplicación del hidrocarburo aromático policíclico 7,12-dimetil-1,2-benzatraceno (DMBA) sobre la mucosa oral del hámster y del cobaya. Rev Esp Patol. 2009;42:287-95.

[6]. Nagini S, Kowshik J. The Hamster Buccal Pouch Model of Oral Carcinogenesis. Methods Mol Biol. 2016;1422:341-50. doi: 10.1007/978-1-4939-3603-8_29. PMID: 27246045.

[7]. Ribeiro DR, Alves ÂV, dos Santos EP, Padilha FF, Gomes MZ, Rabelo AS, Cardoso JC, Massarioli AP, de Alencar SM, de Albuquerque-Júnior RL. Inhibition of DMBA-induced Oral Squamous Cells Carcinoma Growth by Brazilian Red Propolis in Rodent Model. Basic Clin Pharmacol Toxicol. 2015;117(2):85-95. doi: 10.1111/bcpt.12374. PMID: 25556639.

[8]. Ribeiro DR, Alves ÂV, dos Santos EP, Padilha FF, Gomes MZ, Rabelo AS, Cardoso JC, Massarioli AP, de Alencar SM, de Albuquerque-Júnior RL. Inhibition of DMBA-induced Oral Squamous Cells Carcinoma Growth by Brazilian Red Propolis in Rodent Model. Basic Clin Pharmacol Toxicol. 2015;117(2):85-95. doi: 10.1111/bcpt.12374. PMID: 25556639.

[9]. Kim BR, Seo JY, Sung MK, Park JH, Suh HJ, Liu KH, Kim JS. Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis by glyceollins. Mol Nutr Food Res. 2015 May;59(5):907-17. doi: 10.1002/mnfr.201400726. Epub 2015 Mar 16. PMID: 25641514.

[10]. Odajima T, Solt DB, Solt LC. Persistence of gamma-glutamyl transpeptidase-positive foci during hamster buccal pouch carcinogenesis. Cancer Res. 1984;44(5):2062-7. PMID: 6143614.

[11]. Calderon-Solt L, Solt DB. Gamma-glutamyl transpeptidase in precancerous lesions and carcinomas of oral, pharyngeal, and laryngeal mucosa. Cancer. 1985;56(1):138-43. doi: 10.1002/1097-0142(19850701)56:1<138:aid-cncr2820560122>3.0.co;2-4. PMID: 2408724.

[12]. Rutenburg AM, Kim H, Fischbein JW, Hanker JS, Wasserkrug HL, Seligman AM. Histochemical and ultrastructural demonstration of gamma-glutamyl transpeptidase activity. J Histochem Cytochem. 1969;17(8):517-26. doi: 10.1177/17.8.517. PMID: 5816239.

[13]. Sporn MB, Suh N. Chemoprevention: an essential approach to controlling cancer. Nat Rev Cancer. 2002;2(7):537-43. doi: 10.1038/nrc844. PMID: 12094240.

[14]. Serrano D, Lazzeroni M, Bonanni B. Cancer chemoprevention: Much has been done, but there is still much to do. State of the art and possible new approaches. Mol Oncol. 2015;9(5):1008-17. doi: 10.1016/j.molonc.2014.12.006. PMID: 25556583; PMCID: PMC5528739.

[15]. Pavia M, Pileggi C, Nobile CG, Angelillo IF. Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. Am J Clin Nutr. 2006;83(5):1126-34. doi: 10.1093/ajcn/83.5.1126. PMID: 16685056.

[16]. Wu QJ, Xie L, Zheng W, Vogtmann E, Li HL, Yang G, Ji BT, Gao YT, Shu XO, Xiang YB. Cruciferous vegetables consumption and the risk of female lung cancer: a prospective study and a meta-analysis. Ann Oncol. 2013;24(7):1918-1924. doi: 10.1093/annonc/mdt119. PMID: 23553059; PMCID: PMC3690909.

[17]. Stoner GD, Morrissey DT, Heur YH, Daniel EM, Galati AJ, Wagner SA. Inhibitory effects of phenethyl isothiocyanate on N-nitrosobenzylmethylamine carcinogenesis in the rat esophagus. Cancer Res. 1991 Apr 15;51(8):2063-8. PMID: 2009525.

[18]. Stoner GD, Morse MA. Isothiocyanates and plant polyphenols as inhibitors of lung and esophageal cancer. Cancer Lett. Mar 19;114(1-2):113-9. doi: 10.1016/s0304-3835(97)04639-9. PMID: 9103268.

[19]. Stoner GD, Kresty LA, Carlton PS, Siglin JC, Morse MA. Isothiocyanates and freeze-dried strawberries as inhibitors of esophageal cancer. Toxicol Sci. 1999;52(2 Suppl):95-100. doi: 10.1093/toxsci/52.2.95. PMID: 10630596.

[20]. Gupta P, Kim B, Kim SH, Srivastava SK. Molecular targets of isothiocyanates in cancer: recent advances. Mol Nutr Food Res. 2014;58(8):1685-707. doi: 10.1002/mnfr.201300684. PMID: 24510468; PMCID: PMC4122603.

[21]. Yeh YT, Yeh H, Su SH, Lin JS, Lee KJ, Shyu HW, Chen ZF, Huang SY, Su SJ. Phenethyl isothiocyanate induces DNA damage-associated G2/M arrest and subsequent apoptosis in oral cancer cells with varying p53 mutations. Free Radic Biol Med. 2014;74:1-13. doi: 10.1016/j.freeradbiomed.2014.06.008. PMID: 24952138.

[22]. Kim EJ, Hong JE, Eom SJ, Lee JY, Park JH. Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. Breast Cancer Res Treat. 2011;130(1):61-71. doi: 10.1007/s10549-010-1299-8. PMID: 21170677.

[23]. Kim SH, Sehrawat A, Singh SV. Dietary chemopreventative benzyl isothiocyanate inhibits breast cancer stem cells in vitro and in vivo. Cancer Prev Res (Phila). 2013;6(8):782-90. doi: 10.1158/1940-6207.CAPR-13-0100. PMID: 23661606; PMCID: PMC3737245.

[24]. Rao CV. Benzyl isothiocyanate: double trouble for breast cancer cells. Cancer Prev Res (Phila). 2013;6(8):760-3. doi: 10.1158/1940-6207.CAPR-13-0242. PMID: 23842793.

[25]. Chiao JW, Wu H, Ramaswamy G, Conaway CC, Chung FL, Wang L, Liu D. Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis. 2004;25(8):1403-8. doi: 10.1093/carcin/bgh136.PMID: 15016658.

[26]. Sahu RP, Zhang R, Batra S, Shi Y, Srivastava SK. Benzyl isothiocyanate-mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of MAPK in human pancreatic cancer cells. Carcinogenesis. 2009;30(10):1744-53. doi: 10.1093/carcin/bgp157.. PMID: 19549704; PMCID: PMC2757546.

[27]. Abbaoui B, Lucas CR, Riedl KM, Clinton SK, Mortazavi A. Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention. Mol Nutr Food Res. 2018;62(18):e1800079. doi: 10.1002/mnfr.201800079. PMID: 30079608; PMCID: PMC6196731.

[28]. Solt DB, Chang Kw, Helenowski I, Rademaker AW. Phenethyl isothiocyanate inhibits nitrosamine carcinogenesis in a model for study of oral cancer chemoprevention. Cancer Lett. 2003; 202(2):147-52. doi: 10.1016/j.canlet.2003.08.021. PMID: 14643444.

[29]. Chikara S, Nagaprashantha LD, Singhal J, Horne D, Awasthi S, Singhal SS. Oxidative stress and dietary phytochemicals: Role in cancer chemoprevention and treatment. Cancer Lett. 2018;413:122-134. doi: 10.1016/j.canlet.2017.11.002. PMID: 29113871.

[30]. Gründemann C, Huber R. Chemoprevention with isothiocyanates - From bench to bedside. Cancer Lett. 2018;414:26-33. doi: 10.1016/j.canlet.2017.10.033. PMID: 29111351.

[31]. Gupta P, Wright SE, Kim SH, Srivastava SK. Phenethyl isothiocyanate: a comprehensive review of anti-cancer mechanisms. Biochim Biophys Acta. 2014;1846(2):405-24. doi: 10.1016/j.bbcan.2014.08.003. PMID: 25152445; PMCID: PMC4260992.

[32]. Moral R, Solanas M, García G, Grau L, Vela E, Escrich R, Escrich E. High corn oil and extra virgin olive oil diets have different effects on the expression of differentiation-related genes in experimental mammary tumors. Oncol Rep. 2008;20:429-5.

[33]. Soto-Castillo JJ, Ortega-Medina I. Carcinogenesis experimental con 7,12-dimetilbenzantraceno (DMBA) y su inhibición con aceite de olive virgin extra y dieta con aceitunas maduras (variedad Picual). Rev Esp Pat. 2017; 50:82-88.

[34]. Soto-Castillo JJ, Ortega-Medina I. Chapter: Experimental Carcinogenesis with 7,12-Dimethylbenz(a)Anthrazene (DMBA) and Its Inhibition with Extra Virgin Olive Oil and a Diet of Mature Olives (Picual Variety). In Olive Oil – New Perpectives and Applications. IntechOpen. March 4th 2021.

[35]. Head and Neck. Oral Cavity. AJCC Cancer Staging Manual, 8th Edition. New York. Springer 2017. (Edition S, Edge S, Byrd D. AJCC cancer staging manual. AJCC cancer staging manual. 2017. ISBN: 978-3-319-40617-6 https://link.springer.com/book/9783319406176
How to Cite
MORALES-HERRERO, María; ORTEGA-MEDINA, Isicio. Experimental carcinogenesis with 7,12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates.. Journal of Oral Research, [S.l.], v. 11, n. 4, p. 1-13, aug. 2022. ISSN 0719-2479. Available at: <https://www.joralres.com/index.php/JOralRes/article/view/joralres.2022.047>. Date accessed: 28 sep. 2023. doi: https://doi.org/10.17126/joralres.2022.047.