CHEMOPROTECTIVE EFFECT OF MELATONIN ON DMBA/CROTON OIL INDUCED CARCINOGENESIS IN SKIN OF SWISS ALBINO MICE
Keywords:
KEYWORDS: DMBA/Croton Oil, Skin Carcinogenesis, Melatonin, Antioxidants.
Abstract
ABSTRACT
Melatonin, a hormone secreted by the pineal gland, is known to have anti-mutagenic, antioxidant and oncostatic functions. This beneficial action of melatonin has been explained in terms of its ability to scavenge free radicals and the activities of anti-oxidant enzymes. The present study was carried out to evaluate the anti-tumor activity of melatonin on the two stage process of skin carcinogenesis, A significant reduction in tumor incidence, tumor burden, tumor yield, and cumulative number of papilloma was observed in mice treated with 10mg/kg of melatonin as compared to the positive control group treated with DMBA plus croton oil. Furthermore, Histopathological alterations in the carcinogen-treated control animals were also observed in the form of epidermal hyperplasia, keratinized pearl formation, and acanthosis in skin and tumors, whereas these were found to be reduced significantly in melatonin group were administrated before DMBA administration. The results thus can be suggested that melatonin may function as an endogenous anti-mutagenic and oncostatic agent
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References
REFERENCES
Mestas, J., & Hughes, C. C. (2004). Of mice and not men: differences between mouse and human immunology. The Journal of Immunology, 172(5), 2731-2738.
Balmain, A., & Brown, K. (1988). Oncogene activation in chemical carcinogenesis. In Advances in cancer research (Vol. 51, pp. 147-182). Academic Press.
Rastogi, S., Shukla, Y., Paul, B. N., Chowdhuri, D. K., Khanna, S. K., & Das, M. (2007). Protective effect of Ocimum sanctum on 3-methylcholanthrene, 7, 12-dimethylbenz (a) anthracene and aflatoxin B1 induced skin tumorigenesis in mice. Toxicology and applied pharmacology, 224(3), 228-240.
Tiwari, P., Sahay, S., Pandey, M., Qadri, S. S., & Gupta, K. P. (2015). Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events. Chemico-biological interactions, 226, 1-11.
Blask, D. E., Dauchy, R. T., & Sauer, L. A. (2005). Putting cancer to sleep at night. Endocrine, 27(2), 179-188.
Viswanathan, A. N., Hankinson, S. E., & Schernhammer, E. S. (2007). Night shift work and the risk of endometrial cancer. Cancer research, 67(21), 10618-10622.
Grant, S. G., Melan, M. A., Latimer, J. J., & Witt-Enderby, P. A. (2009). Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives. Expert reviews in molecular medicine, 11.
Reiter, R. J., Rosales-Corral, S., Tan, D. X., Jou, M. J., Galano, A., & Xu, B. (2017). Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cellular and molecular life sciences, 74(21), 3863-3881.
Reiter, R. J. (1991). Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrine reviews, 12(2), 151-180.
Reiter, R. J. (1991). Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrine reviews, 12(2), 151-180.
Tan, D. X., Manchester, L. C., Hardeland, R., Lopez‐Burillo, S., Mayo, J. C., Sainz, R. M., & Reiter, R. J. (2003). Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. Journal of pineal research, 34(1), 75-78.
Hardeland, R., Tan, D. X., & Reiter, R. J. (2009). Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines. Journal of pineal research, 47(2), 109-126.
Luchetti, F., Canonico, B., Betti, M., Arcangeletti, M., Pilolli, F., Piroddi, M., ... & Galli, F. (2010). Melatonin signaling and cell protection function. The FASEB Journal, 24(10), 3603-3624.
Vijayalaxmi, Thomas Jr, C. R., Reiter, R. J., & Herman, T. S. (2002). Melatonin: from basic research to cancer treatment clinics. Journal of Clinical Oncology, 20(10), 2575-2601.
Srinivasan, V., Spence, D. W., Pandi-Perumal, S. R., Trakht, I., & Cardinali, D. P. (2008). Therapeutic actions of melatonin in cancer: possible mechanisms. Integrative cancer therapies, 7(3), 189-203.
Reiter, R. J., Tan, D. X., Mayo, J. C., Sainz, R. M., Leon, J., & Czarnocki, Z. (2003). Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. ACTA BIOCHIMICA POLONICA-ENGLISH EDITION-, 50(4), 1129-1146..
Tan, D. X., Manchester, L. C., Terron, M. P., Flores, L. J., & Reiter, R. J. (2007). One molecule, many derivatives: a never‐ending interaction of melatonin with reactive oxygen and nitrogen species?. Journal of pineal research, 42(1), 28-42.
Galano, A., Tan, D. X., & Reiter, R. J. (2011). Melatonin as a natural ally against oxidative stress: a physicochemical examination. Journal of pineal research, 51(1), 1-16.
Galano, A., Tan, D. X., & Reiter, R. J. (2013). On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK. Journal of pineal research, 54(3), 245-257.
Maitra, S., Bhattacharya, D., Das, S., & Bhattacharya, S. (2019). Melatonin and its anti-glioma functions: a comprehensive review. Reviews in the neurosciences.
Jung, B., & Ahmad, N. (2006). Melatonin in cancer management: progress and promise. Cancer research, 66(20), 9789-9793.
Tian, X., Wang, F., Zhang, L., Ji, P., Wang, J., Lv, D., ... & Liu, G. (2017). Melatonin promotes the in vitro development of microinjected pronuclear mouse embryos via its anti-oxidative and anti-apoptotic effects. International journal of molecular sciences, 18(5), 988.
Reiter, R. J., Rosales-Corral, S., Tan, D. X., Jou, M. J., Galano, A., & Xu, B. (2017). Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cellular and molecular life sciences, 74(21), 3863-3881.
Reiter, R. J., Tan, D. X., Manchester, C., Burillo, S. L., Juan, M. S., & Mayo, C. (2003). Melatonin: detoxification of oxygen and nitrogen-based toxic reactants. In Developments in Tryptophan and Serotonin Metabolism (pp. 539-548). Springer, Boston, MA.
Slominski, A., Fischer, T. W., Zmijewski, M. A., Wortsman, J., Semak, I., Zbytek, B., ... & Tobin, D. J. (2005). On the role of melatonin in skin physiology and pathology. Endocrine, 27(2), 137-147.
Kim, T. K., Kleszczyński, K., Janjetovic, Z., Sweatman, T., Lin, Z., Li, W., ... & Slominski, A. T. (2013). Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells. The FASEB Journal, 27(7), 2742-2755.
Hill, S. M., Frasch, T., Xiang, S., Yuan, L., Duplessis, T., & Mao, L. (2009). Molecular mechanisms of melatonin anticancer effects. Integrative cancer therapies, 8(4), 337-346.
Pandey, S., & Agrawal, R. C. (2009). Effect of bauhinia variegate bark extract on DMBA-induced mouse skin carcinogenesis: a preliminary study. Global Journal of Pharmacology, 3(3), 158-162.
Duncan DB (1955). Multiple range and multiple F tests. Biometrics; 11: 1-42.
SPSS (2013). Statistical Package for Social Sciences (SPSS) software Ltd. IBM, Inc., Ver. 21, UK.
Wu, X., & Pandolfi, P. P. (2001). Mouse models for multistep tumorigenesis. Trends in cell biology, 11, S2-S9.
Coghlan, L. G., Gimenez-Conti, I., Kleiner, H. E., Fischer, S. M., Rundhaug, J. E., Conti, C. J., ... & DiGiovanni, J. (2000). Development and initial characterization of several new inbred strains of SENCAR mice for studies of multistage skin carcinogenesis. Carcinogenesis, 21(4), 641-646.
Ward, J. M., Rehm, S., Devor, D., Hennings, H., & Wenk, M. L. (1986). Differential carcinogenic effects of intraperitoneal initiation with 7, 12-dimethylbenz (a) anthracene or urethane and topical promotion with 12-O-tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice. Environmental health perspectives, 68, 61-68.
Walentinsson, A., & Levan, G. (2001). Ras gene mutations in 7, 12-dimethylbenz [a] anthracene (DMBA)-induced rat sarcomas. Cancer letters, 166(1), 47-53.
Russo, J., Tay, L. K., & Russo, I. H. (1982). Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast cancer research and treatment, 2(1), 5-73.
Daniel, F. B., & Joyce, N. J. (1983). DNA adduct formation by 7, 12-dimethylbenz [a] anthracene and its noncarcinogenic 2-fluoro analogue in female Sprague-Dawley rats. Journal of the National Cancer Institute, 70(1), 111-118.35.
Katz, I. S. S., Albuquerque, L. L., Suppa, A. P., da Silva, G. B., Jensen, J. R., Borrego, A., ... & Borelli, P. (2016). 7, 12-Dimethylbenz (a) anthracene-induced genotoxicity on bone marrow cells from mice phenotypically selected for low acute inflammatory response. DNA repair, 37, 43-52.
Bizub, D., Wood, A. W., & Skalka, A. M. (1986). Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. Proceedings of the National Academy of Sciences, 83(16), 6048-6052.
Man’cheva, T. A., Demidov, D. V., Plotnikova, N. A., Kharitonova, T. V., Pashkevich, I. V., & Anisimov, V. N. (2011). Melatonin and metformin inhibit skin carcinogenesis and lipid peroxidation induced by benz (a) pyrene in female mice. Bulletin of experimental biology and medicine, 151(3), 363-365.
Srinivasan, V., Spence, D. W., Pandi-Perumal, S. R., Trakht, I., & Cardinali, D. P. (2008). Therapeutic actions of melatonin in cancer: possible mechanisms. Integrative cancer therapies, 7(3), 189-203.
Venegas, C., García, J. A., Escames, G., Ortiz, F., López, A., Doerrier, C., ... & Acuña‐Castroviejo, D. (2012). Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. Journal of pineal research, 52(2), 217-227.
Hanikoglu, F., Cort, A., Ozben, H., Hanikoglu, A., & Ozben, T. (2015). Epoxomicin sensitizes resistant osteosarcoma cells to Trail induced apoptosis. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 15(4), 527-533.
Gatti, G., Lucini, V., Dugnani, S., Calastretti, A., Spadoni, G., Bedini, A., ... & Bevilacqua, A. (2017). Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells. Oncotarget, 8(40), 68338.
Junqueira, L. C. U., & Carneiro, J. (2005). Basic histology: text & atlas. McGraw-Hill Professional. 360-370.
Casanova, M. L., Blázquez, C., Martínez-Palacio, J., Villanueva, C., Fernández-Aceñero, M. J., Huffman, J. W., ... & Guzmán, M. (2003). Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. The Journal of clinical investigation, 111(1), 43-50.
Majed, F., Nafees, S., Rashid, S., Ali, N., Hasan, S. K., Ali, R., ... & Sultana, S. (2015). Terminalia chebula attenuates DMBA/Croton Oil-Induced oxidative stress and inflammation in Swiss albino mouse skin. Toxicology international, 22(1), 21.
Gopalakrishnan, T., Ganapathy, S., Veeran, V., & Namasivayam, N. (2019). Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events. Biomedicine & Pharmacotherapy, 111, 178-187.
Srinivasan, V., Spence, D. W., Trakht, I., Pandi-Perumal, S. R., Cardinali, D. P., & Maestroni, G. J. (2008). Immunomodulation by melatonin: its significance for seasonally occurring diseases. Neuroimmunomodulation, 15(2), 93-101.
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Mestas, J., & Hughes, C. C. (2004). Of mice and not men: differences between mouse and human immunology. The Journal of Immunology, 172(5), 2731-2738.
Balmain, A., & Brown, K. (1988). Oncogene activation in chemical carcinogenesis. In Advances in cancer research (Vol. 51, pp. 147-182). Academic Press.
Rastogi, S., Shukla, Y., Paul, B. N., Chowdhuri, D. K., Khanna, S. K., & Das, M. (2007). Protective effect of Ocimum sanctum on 3-methylcholanthrene, 7, 12-dimethylbenz (a) anthracene and aflatoxin B1 induced skin tumorigenesis in mice. Toxicology and applied pharmacology, 224(3), 228-240.
Tiwari, P., Sahay, S., Pandey, M., Qadri, S. S., & Gupta, K. P. (2015). Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events. Chemico-biological interactions, 226, 1-11.
Blask, D. E., Dauchy, R. T., & Sauer, L. A. (2005). Putting cancer to sleep at night. Endocrine, 27(2), 179-188.
Viswanathan, A. N., Hankinson, S. E., & Schernhammer, E. S. (2007). Night shift work and the risk of endometrial cancer. Cancer research, 67(21), 10618-10622.
Grant, S. G., Melan, M. A., Latimer, J. J., & Witt-Enderby, P. A. (2009). Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives. Expert reviews in molecular medicine, 11.
Reiter, R. J., Rosales-Corral, S., Tan, D. X., Jou, M. J., Galano, A., & Xu, B. (2017). Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cellular and molecular life sciences, 74(21), 3863-3881.
Reiter, R. J. (1991). Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrine reviews, 12(2), 151-180.
Reiter, R. J. (1991). Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocrine reviews, 12(2), 151-180.
Tan, D. X., Manchester, L. C., Hardeland, R., Lopez‐Burillo, S., Mayo, J. C., Sainz, R. M., & Reiter, R. J. (2003). Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. Journal of pineal research, 34(1), 75-78.
Hardeland, R., Tan, D. X., & Reiter, R. J. (2009). Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines. Journal of pineal research, 47(2), 109-126.
Luchetti, F., Canonico, B., Betti, M., Arcangeletti, M., Pilolli, F., Piroddi, M., ... & Galli, F. (2010). Melatonin signaling and cell protection function. The FASEB Journal, 24(10), 3603-3624.
Vijayalaxmi, Thomas Jr, C. R., Reiter, R. J., & Herman, T. S. (2002). Melatonin: from basic research to cancer treatment clinics. Journal of Clinical Oncology, 20(10), 2575-2601.
Srinivasan, V., Spence, D. W., Pandi-Perumal, S. R., Trakht, I., & Cardinali, D. P. (2008). Therapeutic actions of melatonin in cancer: possible mechanisms. Integrative cancer therapies, 7(3), 189-203.
Reiter, R. J., Tan, D. X., Mayo, J. C., Sainz, R. M., Leon, J., & Czarnocki, Z. (2003). Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. ACTA BIOCHIMICA POLONICA-ENGLISH EDITION-, 50(4), 1129-1146..
Tan, D. X., Manchester, L. C., Terron, M. P., Flores, L. J., & Reiter, R. J. (2007). One molecule, many derivatives: a never‐ending interaction of melatonin with reactive oxygen and nitrogen species?. Journal of pineal research, 42(1), 28-42.
Galano, A., Tan, D. X., & Reiter, R. J. (2011). Melatonin as a natural ally against oxidative stress: a physicochemical examination. Journal of pineal research, 51(1), 1-16.
Galano, A., Tan, D. X., & Reiter, R. J. (2013). On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK. Journal of pineal research, 54(3), 245-257.
Maitra, S., Bhattacharya, D., Das, S., & Bhattacharya, S. (2019). Melatonin and its anti-glioma functions: a comprehensive review. Reviews in the neurosciences.
Jung, B., & Ahmad, N. (2006). Melatonin in cancer management: progress and promise. Cancer research, 66(20), 9789-9793.
Tian, X., Wang, F., Zhang, L., Ji, P., Wang, J., Lv, D., ... & Liu, G. (2017). Melatonin promotes the in vitro development of microinjected pronuclear mouse embryos via its anti-oxidative and anti-apoptotic effects. International journal of molecular sciences, 18(5), 988.
Reiter, R. J., Rosales-Corral, S., Tan, D. X., Jou, M. J., Galano, A., & Xu, B. (2017). Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cellular and molecular life sciences, 74(21), 3863-3881.
Reiter, R. J., Tan, D. X., Manchester, C., Burillo, S. L., Juan, M. S., & Mayo, C. (2003). Melatonin: detoxification of oxygen and nitrogen-based toxic reactants. In Developments in Tryptophan and Serotonin Metabolism (pp. 539-548). Springer, Boston, MA.
Slominski, A., Fischer, T. W., Zmijewski, M. A., Wortsman, J., Semak, I., Zbytek, B., ... & Tobin, D. J. (2005). On the role of melatonin in skin physiology and pathology. Endocrine, 27(2), 137-147.
Kim, T. K., Kleszczyński, K., Janjetovic, Z., Sweatman, T., Lin, Z., Li, W., ... & Slominski, A. T. (2013). Metabolism of melatonin and biological activity of intermediates of melatoninergic pathway in human skin cells. The FASEB Journal, 27(7), 2742-2755.
Hill, S. M., Frasch, T., Xiang, S., Yuan, L., Duplessis, T., & Mao, L. (2009). Molecular mechanisms of melatonin anticancer effects. Integrative cancer therapies, 8(4), 337-346.
Pandey, S., & Agrawal, R. C. (2009). Effect of bauhinia variegate bark extract on DMBA-induced mouse skin carcinogenesis: a preliminary study. Global Journal of Pharmacology, 3(3), 158-162.
Duncan DB (1955). Multiple range and multiple F tests. Biometrics; 11: 1-42.
SPSS (2013). Statistical Package for Social Sciences (SPSS) software Ltd. IBM, Inc., Ver. 21, UK.
Wu, X., & Pandolfi, P. P. (2001). Mouse models for multistep tumorigenesis. Trends in cell biology, 11, S2-S9.
Coghlan, L. G., Gimenez-Conti, I., Kleiner, H. E., Fischer, S. M., Rundhaug, J. E., Conti, C. J., ... & DiGiovanni, J. (2000). Development and initial characterization of several new inbred strains of SENCAR mice for studies of multistage skin carcinogenesis. Carcinogenesis, 21(4), 641-646.
Ward, J. M., Rehm, S., Devor, D., Hennings, H., & Wenk, M. L. (1986). Differential carcinogenic effects of intraperitoneal initiation with 7, 12-dimethylbenz (a) anthracene or urethane and topical promotion with 12-O-tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice. Environmental health perspectives, 68, 61-68.
Walentinsson, A., & Levan, G. (2001). Ras gene mutations in 7, 12-dimethylbenz [a] anthracene (DMBA)-induced rat sarcomas. Cancer letters, 166(1), 47-53.
Russo, J., Tay, L. K., & Russo, I. H. (1982). Differentiation of the mammary gland and susceptibility to carcinogenesis. Breast cancer research and treatment, 2(1), 5-73.
Daniel, F. B., & Joyce, N. J. (1983). DNA adduct formation by 7, 12-dimethylbenz [a] anthracene and its noncarcinogenic 2-fluoro analogue in female Sprague-Dawley rats. Journal of the National Cancer Institute, 70(1), 111-118.35.
Katz, I. S. S., Albuquerque, L. L., Suppa, A. P., da Silva, G. B., Jensen, J. R., Borrego, A., ... & Borelli, P. (2016). 7, 12-Dimethylbenz (a) anthracene-induced genotoxicity on bone marrow cells from mice phenotypically selected for low acute inflammatory response. DNA repair, 37, 43-52.
Bizub, D., Wood, A. W., & Skalka, A. M. (1986). Mutagenesis of the Ha-ras oncogene in mouse skin tumors induced by polycyclic aromatic hydrocarbons. Proceedings of the National Academy of Sciences, 83(16), 6048-6052.
Man’cheva, T. A., Demidov, D. V., Plotnikova, N. A., Kharitonova, T. V., Pashkevich, I. V., & Anisimov, V. N. (2011). Melatonin and metformin inhibit skin carcinogenesis and lipid peroxidation induced by benz (a) pyrene in female mice. Bulletin of experimental biology and medicine, 151(3), 363-365.
Srinivasan, V., Spence, D. W., Pandi-Perumal, S. R., Trakht, I., & Cardinali, D. P. (2008). Therapeutic actions of melatonin in cancer: possible mechanisms. Integrative cancer therapies, 7(3), 189-203.
Venegas, C., García, J. A., Escames, G., Ortiz, F., López, A., Doerrier, C., ... & Acuña‐Castroviejo, D. (2012). Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. Journal of pineal research, 52(2), 217-227.
Hanikoglu, F., Cort, A., Ozben, H., Hanikoglu, A., & Ozben, T. (2015). Epoxomicin sensitizes resistant osteosarcoma cells to Trail induced apoptosis. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 15(4), 527-533.
Gatti, G., Lucini, V., Dugnani, S., Calastretti, A., Spadoni, G., Bedini, A., ... & Bevilacqua, A. (2017). Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells. Oncotarget, 8(40), 68338.
Junqueira, L. C. U., & Carneiro, J. (2005). Basic histology: text & atlas. McGraw-Hill Professional. 360-370.
Casanova, M. L., Blázquez, C., Martínez-Palacio, J., Villanueva, C., Fernández-Aceñero, M. J., Huffman, J. W., ... & Guzmán, M. (2003). Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. The Journal of clinical investigation, 111(1), 43-50.
Majed, F., Nafees, S., Rashid, S., Ali, N., Hasan, S. K., Ali, R., ... & Sultana, S. (2015). Terminalia chebula attenuates DMBA/Croton Oil-Induced oxidative stress and inflammation in Swiss albino mouse skin. Toxicology international, 22(1), 21.
Gopalakrishnan, T., Ganapathy, S., Veeran, V., & Namasivayam, N. (2019). Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events. Biomedicine & Pharmacotherapy, 111, 178-187.
Srinivasan, V., Spence, D. W., Trakht, I., Pandi-Perumal, S. R., Cardinali, D. P., & Maestroni, G. J. (2008). Immunomodulation by melatonin: its significance for seasonally occurring diseases. Neuroimmunomodulation, 15(2), 93-101.
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Published
2020-06-07
How to Cite
AMIN OMAR, S. M., & AMIN MOHAMMED, B. M. (2020). CHEMOPROTECTIVE EFFECT OF MELATONIN ON DMBA/CROTON OIL INDUCED CARCINOGENESIS IN SKIN OF SWISS ALBINO MICE. Journal of Duhok University, 23(1), 115-125. https://doi.org/10.26682/sjuod.2020.23.1.12
Section
Pure and Engineering Sciences
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