The Influence of DMBA (7,12-dimethylbenz-[a]anthracene) Regimen In The Development of Mammae Carcinogénesis on Sprague Dawley Female Rat

Agung Eru Wibowo, Sriningsih Sriningsih, Puspita Eka Wuyung, Raafqi Ranasasmita

Abstract


There are many methods for development of mammae cancer animal model, one of which is chemical induction using carcinogenic agent, DMBA. This research aimed to explore the influence of dose and time regimens of DMBA on development of mammae carcinogenesis on Sprague dawley female rats. The first study was 50 rats treated with 20 mg/kg bw of DMBA orally for eleven times at twice a week. Morphological evaluations were conducted with mammae palpation for 15 weeks and then all of rats were sacrificed for collecting mammae organs for histological analysis using hematoxylin-eosin staining. The results showed that the first and the latest nodules appeared at the fourth-week and the fourteenth-week after ending DMBA induction, respectively, in which the most often nodule appearances were at the seventh-week. The number of nodule incidence and multiplicity were by 74% and 2 noduls/rat, respectively. Histological analysis of mammae glands determined that they fell under in Ductal Carcinoma Invasive (DCIV) category. The second study was 25 rats gavaged orally with DMBA at dose 20 mg/kg bw for five times every three days. After palpating for 15 weeks, the results showed that no nodule was observed but the histological analysis demonstrated developing of mammae gland carcinogenesis reaching about 60% Ductal Carcinoma Insitu (DCIS) and 40% Ductal Carcinoma Invasive (DCIV) stages. Based on the results of this study can be concluded that the dose and frequency of DMBA will affect the successful development of mammary gland carcinogenesis. In DMBA induction with low frequency, no data showed the incidence and multiplicity of tumor, but histopathologic level carcinogenesis can be distinguished. In DMBA induction with high frequency, incidence and multiplicity of tumor data can be obtained but can not be distinguished histopathologically.

Keywords: DMBA, doses, carcinogenesis, mammae, histopatology


Full Text:

PDF

References


Androutsopoulos V.P., Tsatsakis A.M., and Spandidos D.A., 2009, Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention, BMC Cancer 9:187.

Gear RB, Yan M, Schneider J, Succop P, Heffelfinger SC, Clegg DJ. Charles River Sprague Dawley Rats Lack Early Age-Dependent Susceptibility to DMBA-Induced Mammary Carcinogenesis. Int J Biol Sciences. 2007; 3(7):408-16.

Hakkak R., Holley A.W., MacLeod S.L., Simpson P.M., Fuchs G.J., Jo C.H., Kieber-Emmons T., and Korourian S., 2005, Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female Zucker rats, Breast Cancer Research, 7:R627-R633.

Kubatka P, Ahlersova E, Ahlers I, Bojkova B, Kalicka K, Adamekova E, et al. Variability of Mammary Carcinogenesis Induction in Female Sprague-Dawley and Wistar:Han Rats: the Effect of Season and Age. Physiol Res. 2002;5:633-40.

Lenoir V, Canonico MBY, Perrin MH, Martin A, Scholler R, et al. Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague–Dawley rat. Breast Cancer Res. 2005; 7:R470-R476.

Meiyanto E, Tasminatun S, Susilowati S, Murwanti R dan Sugiyanto. Efek kemopreventif ekstrak etanolik Gynura procumbens (Lour), Merr pada karsinogenesis kanker payudara tikus. Majalah Farmasi Indonesia. 2007; 18(3).

Pocar P, Fischer B, Klonisch T and Klonisch SH. P. Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction, Review, Society for Reproduction and Fertility. 2005; 28, 1741–7899.

RSKD. Laporan Bagian Rekam Medis RSKD. http://www.dharmais.co.id /index.php /statistic-center.html. accesed on March 31, 2010

Sigma-Aldrich. 2007. 7,12-Dimethylbenz[a] anthracene.http://www.sigmaaldrich.com, accessed on April 27, 2007.

Ting A.Y., Kimler B.F., Fabian C.J., and Petroff B.K., 2007, Characterization of a preclinical model of simultaneous breast and ovarian cancer progression, Carcinogenesis vol.28 no.1 pp.130–135, 2007.

Tsao AS, Kim ES and Hong WK., 2004, Chemoprevention of Cancer, CA Cancer J Clin; 2004;54:150–180.

World Health Organization. The World Health Report 2008 : primary health care now more than ever. www.who.int/entity/whr/2008/08, accesed on August 9, 2009.

Zeiger R.S., Salomon R., Kinoshita N., and Peacock A.C., 1972, The Binding of 9,10-Dimethyl-l,2-benzanthracene to Mouse Epidermal Satellite DNA in Vivo, Cancer Research, 32, 643-647.




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev1iss1pp60-66

Copyright (c) 2017 Indonesian Journal of Cancer Chemoprevention

Indexed by:

                  

               

 

Indonesian Society for Cancer Chemoprevention