Artículos de revistas
Characterization Of Chemically Induced Ovarian Carcinomas In An Ethanol-preferring Rat Model: Influence Of Long-term Melatonin Treatment
Plos One. , v. 8, n. 12, p. - , 2013.
Ovarian cancer is the fourth most common cause of cancer deaths among women, and chronic alcoholism may exert cocarcinogenic effects. Because melatonin (mel) has oncostatic properties, we aimed to investigate and characterize the chemical induction of ovarian tumors in a model of ethanol-preferring rats and to verify the influence of mel treatment on the overall features of these tumors. After rats were selected to receive ethanol (EtOH), they were surgically injected with 100 μg of 7,12-dimethyl-benz[a] anthracene (DMBA) plus sesame oil directly under the left ovarian bursa. At 260 days old, half of the animals received i.p. injections of 200 μg mel/100 g b.w. for 60 days. Four experimental groups were established: Group C, rats bearing ovarian carcinomas (OC); Group C+EtOH, rats voluntarily consuming 10% (v/v) EtOH and bearing OC; Group C+M, rats bearing OC and receiving mel; and Group C+EtOH+M, rats with OC consuming EtOH and receiving mel. Estrous cycle and nutritional parameters were evaluated, and anatomopathological analyses of the ovarian tumors were conducted. The incidence of ovarian tumors was higher in EtOH drinking animals 120 days post-DMBA administration, and mel efficiently reduced the prevalence of some aggressive tumors. Although mel promoted high EtOH consumption, it was effective in synchronizing the estrous cycle and reducing ovarian tumor mass by 20%. While rats in the C group displayed cysts containing serous fluid, C+EtOH rats showed solid tumor masses. After mel treatment, the ovaries of these rats presented as soft and mobile tissues. EtOH consumption increased the incidence of serous papillary carcinomas and sarcomas but not clear cell carcinomas. In contrast, mel reduced the incidence of sarcomas, endometrioid carcinomas and cystic teratomas. Combination of DMBA with EtOH intake potentiated the incidence of OC with malignant histologic subtypes. We concluded that mel reduces ovarian masses and the incidence of adenocarcinomas in ethanol-deprived rats. © 2013 Chuffa et al.812Stakleff, K.D.S., Von Gruenigen, V.E., Rodent models for ovarian cancer research (2003) International Journal of Gynecological Cancer, 13 (4), pp. 405-412. , DOI 10.1046/j.1525-1438.2003.13317.xVanderhyden, B.C., Loss of ovarian function and the risk of ovarian cancer (2005) Cell Tiss Res, 322, pp. 117-124Chien, J.R., Aletti, G., Bell, D.A., Keeney, G.L., Shridhar, V., Hartmann, L.C., Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer (2007) Journal of Cellular Biochemistry, 102 (5), pp. 1117-1129. , DOI 10.1002/jcb.21552Crum, C.P., Drapkin, R., Kindelberger, D., Medeiros, F., Miron, A., Lee, Y., Lessons from BRCA: The tubal fimbria emerges as an origin for pelvic serous cancer (2007) Clinical Medicine and Research, 5 (1), pp. 35-44. , DOI 10.3121/cmr.2007.702Fleming, J.S., Beaugie, C.R., Haviv, I., Chenevix-Trench, G., Tan, O.L., Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: Revisiting old hypotheses (2006) Molecular and Cellular Endocrinology, 247 (1-2), pp. 4-21. , DOI 10.1016/j.mce.2005.09.014, PII S0303720705003400Fathalla, M.F., Incessant ovulation - A factor in ovarian neoplasia? (1971) Lancet, 2, p. 163Konishi, I., Kuroda, H., Mandai, M., Review: Gonadotropins and development of ovarian cancer (1999) Oncology, 57 (SUPPL. 2), pp. 45-48. , DOI 10.1159/000055274Murdoch, W.J., Ovulatory factor in ovarian carcinogenesis (2008) Adv Exp Med Biol, 622, pp. 119-128Ozols, R.F., Rubin, S.C., Thomas, G.M., Robboy, S.J., Epithelial ovarian cancer (2005) Principles and Practice of Gynecologic Oncology, pp. 903-904. , Hoskins WJ, Perez CA, Young RC, Barakat RR, Markman M, Randall ME, editors. fifth ed. Lippincott Williams & Wilkins, Philadelphia, PALynch, H.T., Caseyb, M.J., Snydera, C.L., Bewtrac, C., Lyncha, J.F., Hereditary ovarian carcinoma: Heterogeneity, molecular genetics, pathology, and management (2009) Mol Oncol, 3, pp. 97-137Nishida, T., Sugiyama, T., Kataoka, A., Ushijima, K., Yakushiji, M., Histologic characterization of rat ovarian carcinoma induced by intraovarian insertion of a 7,12-dimethylbenz[a]anthracene-coated suture: Common epithelial tumors of the ovary in rats? (1998) Cancer, 83 (5), pp. 965-970. , DOI 10.1002/(SICI)1097-0142(19980901)83:5<965Nishida, T., Oda, T., Sugiyama, T., Squamous cell carcinoma arising from an epidermoid cyst in the ovary of a rat treated with 7,12-dimethylbenz[a]anthracene (1982) Gann, The Japanese Journal of Cancer Research, 73 (1), pp. 153-157Nishida, T., Sugiyama, T., Katabuchi, H., Histologic origin of rat ovarian cancer induced by direct application of 7,12-dimethylbenz(a)anthracene (1986) Acta Obstetrica et Gynaecologica Japonica, 38 (4), pp. 570-574Mello, N.K., Bree, M.P., Mendelson, J.H., Alcohol self-administration disrupts reproductive function in female macaque monkeys (1983) Science, 221 (4611), pp. 677-679La Vecchia, C., Negri, E., Franceschi, S., Parazzini, F., Gentile, A., Alcohol and epithelial ovarian cancer (1992) J Clin Epidemiol, 45, pp. 1025-1030Rota, M., Pasquali, E., Scotti, L., Pelucchi, C., Tramacere, I., Alcohol drinking and epithelial ovarian cancer risk: A systematic review and meta-analysis (2012) Gynecol Oncol, 125, pp. 758-763Tworoger, S.S., Gertig, D.M., Gates, M.A., Hecht, J.L., Hankinson, S.E., Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer (2008) Cancer, 112 (5), pp. 1169-1177. , DOI 10.1002/cncr.23275Mardones, J., Segovia, R.N., Thirty-two years of selection of rats by ethanol preference: UChA and UChB strains (1983) Neurobehavioral Toxicology and Teratology, 5 (2), pp. 171-178Masana, M.I., Dubocovich, M.L., Melatonin receptor signaling: Finding the path through the dark (2001) Sci STKE, 107, pp. pe39Hill, S.M., Spriggs, L.L., Simon, M.A., Muraoka, H., Blask, D.E., The growth inhibitory action of melatonin on human breast cancer cells is linked to the estrogen response system (1992) Cancer Lett, 64, pp. 249-256Cos, S., González, A., Martínez-Campa, C., Mediavilla, M.D., Alonso-González, C., Melatonin as a selective estrogen enzyme modulator (2008) Curr Cancer Drug Targets, 8, pp. 691-702Reiter, R.J., Mechanisms of cancer inhibition by melatonin (2004) J Pineal Res, 3, pp. 213-214Conti, A., Maestroni, G.J.M., The clinical neuroimmunotherapeutic role of melatonin in oncology (1995) J Pineal Res, 19, pp. 103-110Chada, S., Ramesh, R., Mhashilkar, A.M., Cytokine- and chemokine-based gene therapy for cancer (2003) Current Opinion in Molecular Therapeutics, 5 (5), pp. 463-474Sauer, L.A., Dauchy, R.T., Blask, D.E., Polyunsaturated fatty acids, melatonin, and cancer prevention (2001) Biochemical Pharmacology, 61 (12), pp. 1455-1462. , DOI 10.1016/S0006-2952(01)00634-7, PII S0006295201006347Hoyer, P.B., Davis, J.R., Bedrnicek, J.B., Marion, S.L., Christian, P.J., Ovarian neoplasm development by 7,12-dimethylbenz[a]anthracene (DMBA) in a chemically-induced rat model of ovarian failure (2009) Gynecol Oncol, 112, pp. 610-615Chuffa, L.G., Amorim, J.P., Teixeira, G.R., Mendes, L.O., Fioruci, B.A., Long-term exogenous melatonin treatment modulates overall feed efficiency and protects ovarian tissue against injuries caused by ethanol-induced oxidative stress in adult UChB rats (2011) Alcohol Clin Exp Res, 35, pp. 1498-1508Chuffa, L.G., Seiva, F.R., Favaro, W.J., Teixeira, G.R., Amorim, J.P., Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation (2011) Reprod Biol Endocrinol, 9, p. 108Berstad, P., Ma, H., Bernstein, L., Ursin, G., Alcohol intake and breast cancer risk among young women (2008) Breast Cancer Research and Treatment, 108 (1), pp. 113-120. , DOI 10.1007/s10549-007-9578-8Jacinto-Alemán, L.F., García-Carrancá, A., Leyba-Huerta, E.R., Zenteno-Galindo, E., Jiménez-Farfán, M.D., erbB expression changes in ethanol and 7,12-dimethylbenz(a)anthracene- induced oral carcinogenesis (2013) Med Oral Patol Oral Cir Bucal, 18, pp. e325-e331Seitz, H.K., Wang, X.D., The role of cytochrome P450 2E1 in ethanol-mediated carcinogenesis (2013) Subcell Biochem, 67, pp. 131-143Schouten, L.J., Zeegers, M.P.A., Goldbohm, R.A., Van Den, B.P.A., Alcohol and ovarian cancer risk: Results from the Netherlands Cohort Study (2004) Cancer Causes and Control, 15 (2), pp. 201-209. , DOI 10.1023/B:CACO.0000019512.71560.2bChuffa, L.G., Padovani, C.R., Martinez, F.E., Ovarian structure and hormonal status of the UChA and UChB adult rats in response to ethanol (2009) Maturitas, 62, pp. 21-29Chuffa, L.G., Seiva, F.R., Fávaro, W.J., Amorim, J.P., Teixeira, G.R., Melatonin and ethanol intake exert opposite effects on circulating estradiol and progesterone and differentially regulate sex steroid receptors in the ovaries, oviducts, and uteri of adult rats (2013) Reprod Toxicol, 39, pp. 40-49Wang, Y., Millonig, G., Nair, J., Patsenker, E., Stickel, F., Ethanol-induced cytochrome P-4502E1 causes carcinogenic etheno-DNA lesions in alcoholic liver disease (2009) Hepatology, 50, pp. 453-461Poschl, G., Seitz, H.K., Alcohol and cancer (2004) Alcohol and Alcoholism, 39 (3), pp. 155-165. , DOI 10.1093/alcalc/agh057King, S.M., Hilliard, T.S., Wu, L.Y., Jaffe, R.C., Fazleabas, A.T., The impact of ovulation on fallopian tube epithelial cells: Evaluating three hypotheses connecting ovulation and serous ovarian cancer (2011) Endocr Relat Cancer, 18, pp. 627-642Crespi, F., Influence of melatonin or its antagonism on alcohol consumption in ethanol drinking rats: A behavioral and in vivo voltammetric study (2012) Brain Res, 1452, pp. 39-46Srinivasan, V., Pandi-Perumal, S.R., Brzezinski, A., Bhatnagar, K.P., Cardinali, D.P., Melatonin, immune function and cancer (2011) Recent Pat Endocr Metab Immune Drug Discov, 5, pp. 109-123Lissoni, P., Biochemotherapy with standard chemotherapies plus the pineal hormone melatonin in the treatment of advanced solid neoplasms (2007) Pathol Biol, 55, pp. 201-204Molpeceres, V., Mauriz, J.L., Garcia-Mediavilla, M.V., Gonzalez, P., Barrio, J.P., Gonzalez-Gallego, J., Melatonin is able to reduce the apoptotic liver changes induced by aging via inhibition of the intrinsic pathway of apoptosis (2007) Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 62 (7), pp. 687-695Xi, S.C., Siu, S.W.F., Fong, S.W., Shiu, S.Y.W., Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: Association of antiproliferative action of the pineal hormone with mt1 receptor protein expression (2001) Prostate, 46 (1), pp. 52-61. , DOI 10.1002/1097-0045(200101)46:1<52::AID-PROSPrata, L.M.F., Baracat, E.C., Simoes, M.J., Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: Similarity with polycystic ovary syndrome (2004) Brazilian Journal of Medical and Biological Research, 37 (7), pp. 987-995Chuffa, L.G., Amorim, J.P., Teixeira, G.R., Mendes, L.O., Fioruci, B.A., Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat (2011) Braz J Med Biol Res, 44, pp. 217-223Godwin, A.K., Testa, J.R., Handel, L.M., Liu, Z., Vanderveer, L.A., Spontaneous transformation of rat ovarian surface epithelial cells: Association with cytogenetic changes and implications of repeated ovulation in the etiology of ovarian cancer (1992) J Natl Cancer Inst, 84, pp. 592-601Chien, J.R., Aletti, G., Bell, D.A., Keeney, G.L., Shridhar, V., Hartmann, L.C., Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer (2007) Journal of Cellular Biochemistry, 102 (5), pp. 1117-1129. , DOI 10.1002/jcb.21552Huang, Y., Jiang, W., Wang, Y., Zheng, Y., Cong, Q., Enhanced efficacy and specificity of epithelial ovarian carcinogenesis by embedding a DMBA-coated cloth strip in the ovary of rat (2012) J Ovarian Res, 5, p. 21Crist, K.A., Zhang, Z., You, M., Gunning, W.T., Conran, P.B., Steele, V.E., Lubet, R.A., Characterization of rat ovarian adenocarcinomas developed in response to direct instillation of 7,12-dimethylbenz[a]anthracene (DMBA) coated suture (2005) Carcinogenesis, 26 (5), pp. 951-957. , DOI 10.1093/carcin/bgi039Stewart, S.L., Querec, T.D., Ochman, A.R., Gruver, B.N., Bao, R., Babb, J.S., Wong, T.S., Patriotis, C., Characterization of a carcinogenesis rat model of ovarian preneoplasia and neoplasia (2004) Cancer Research, 64 (22), pp. 8177-8183. , DOI 10.1158/0008-5472.CAN-04-1702Vanderhyden, B.C., Shaw, T.J., Ethier, J.F., Animal models of ovarian cancer (2003) Reprod Biol Endocrinol, 1, p. 67Peres, R., Do Amaral, F.G., Madrigrano, T.C., Scialfa, J.H., Bordin, S., Ethanol consumption and pineal melatonin daily profile in rats (2011) Addict Biol, 16, pp. 580-590Fisher, S.P., Sugden, D., Endogenous melatonin is not obligatory for the regulation of the rat sleep-wake cycle (2010) Sleep, 33, pp. 833-840Treeck, O., Haldar, C., Ortmann, O., Antiestrogens modulate MT1 melatonin receptor expression in breast and ovarian cancer cell lines (2006) Oncol Rep, 15, pp. 231-235