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Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents

Year 2017, Volume: 17 Issue: 1, 18 - 27, 24.04.2017

Abstract

DNA damage due to genotoxic stress is an important type of stress which organisms are exposed during
the their life. The direct-acting alkylating agent methyl methanesulfonate (MMS), is covalently linked to
DNA and cause DNA damage, creating an indirect effect of the alkylating agent cyclophosphamide (CP)
cause to DNA damage by changing the function of cellular proteins. In this study, the effects of
curcumin on MMS and CP treated mice DNA damage, total antioxidant capacity, total oxidant capacity
(oxidative stress index) and genotoxicity markers such as micronucleus index, cell growth arrest and
induced DNA damage, which is Gadd45 and Gadd153 genes expression levels were investigated.
Curcumin reduce DNA damage, the number of micronucleus and oxidative stres occurred by both MMS
and CP induction. Curcumin’s protective effect on DNA damage was provided by inducing Gadd45 and
Gadd153 mRNA expression levels. We could state that curcumin, a phenolic compound show protective
effects before the damage. In brief, curcumin has both antioxidant and antigenotoxic effects.

References

  • Abalea, V., Cillard, J., Dubos, M.P., Sergent, O., Cillard, P., Morel, I. 1999. Repair of iron-induced DNA oxidation by the flavonoid myricetin in primary rat hepatocyte cultures. Free Radical Biolology &Medicine, 26 (11-12), 1457-1466.
  • Agarwal, K.C. 1996. Therapeutic actions of garlic constituents. Medicinal Research Reviews, 16 (1), 111-124.
  • Aggarwal, B.B., Sethi, G., Ahn, K.S., Sandur, S.K., Pandey, M.K., Kunnumakkara, A.B., Sung, B. and Ichikawa, H. 2006. Targeting signal-transducer- and- activator-oftranscription- 3 for prevention and therapy of cancer: modern target but ancient solution. Annals of the New York Academy of the Sciences, 1091, 151-169.
  • Aggarwal, B.B., Gupta, S.C. and Sung, B. 2013a. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. British Journal of Pharmacology, 169 (8), 1672-1692.
  • Anand, P., Sundaram, C., Jhurani, S., Kunnumakkara, A.B. and Aggarwall, B.B. 2008. Curcumin and cancer: an “old-age “ disease with an “age-old” solution. Cancer Letters, 267 (1), 133-164.
  • Araŭjo, C.A. and Leon, L.L. 2001. Biological activities of Curcuma longa L. Memórıas do Instituto Oswaldo Cruz, 96 (5), 723-728.
  • Biswas, J., Roy, S., Mukherjee, S., Sinha, D. and Roy, M. 2010. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice. Asian Pasific Journal of Cancer Prevention, 11 (1), 239-247.
  • Boiteux, S. and Guillet, M. 2004. Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisae. DNA Repair, 3 (1), 1-12.
  • Cicchetti, R., Bari, M. and Argantin, G. 1999. Induction of micronuclei in bone marrow by two pesticides and their differentiation with CREST staining: an in vivo study in mice. Mutation Research, 439 (2), 239-248.
  • Corona, A., Urbina, P., Bobadilla, M., Vargas, J., Ramirez, M.A., Troyo, S., Diaz, P., Corona, J.R. 2007. Protective in vivo effect of curcumin on copper genotoxiciyt evaluated by comet and micronucleus assays. Journal of Applied Genetics, 48 (4), 389-396.
  • Cuce, G., Cetinkaya, S., İsitez, N., Kuccukturk, S., Sozen, M.E., Kalkan, S., Cigerci, İ.H. and Demirel, H.H. 2016. Effects of curcumin on methyl methanesulfonate damage to mouse kidney. Biotechnic & histochemistry, 91 (2), 122-127.
  • Franke, S.I., Pra D., Erdtmann, B., Henriques, J.A. and Silva, J. 2005. Influence of orange juice over the genotoxicity induced by alkylating agents: an in vivo analysis. Mutagenesis, 20 (4), 279-283.
  • Gopal, P., Paul, M. and Pau, S. 2014. Curcumin induces caspase mediated apoptosis in JURKAT cells by disrupting the redox balance. Asian Pacific Journal of Cancer Prevention, 15 (1), 93-100.
  • Horvathova, E., Slamenova, D., Hlincikova, L.,Mandal, T.K., Gabelova, A. and Collins, A.R. 1998. The nature and origin of DNA single-strand breaks determined with the comet assay. Mutation Research, 409, 163- 171.
  • Junk, N., Yi, Y.W., Kim, D., Shong, M., Hong, S.S., Lee, H.S. and Bae, I. 2000. Regulation of Gadd45γ expression by C/EBP. European Journal of Biochemistry, 267 (20), 6180-6187.
  • Kaufmann, L.T., Gierl, M.S., Niehrs, C. 2011. Gadd45a, Gadd45b and Gadd45g expression during mouse embryonic development. Gene Expression Patterns, 11 (8), 465-470.
  • Kunnumakkara, A.B., Bordoloi, D., Padmavathi, G., Monisha, J., Roy, N.K., Prasad, S. and Aggarwal, B.B. 2016. Curcumin, the golden nutraceutical: multitargeting for multiple chronic disease. British Journal of Pharmacology, doi: 10.1111/bph. 13621.
  • Kürkçü, E. 2008. Deneysel Olarak Oluşturulmuş Meme Tümörlerinde Curcumin’in Arginaz Enzim Aktivitesi, Ornitin ve Nitrik Oksit Düzeylerine Etkisi, Yüksek Lisans Tezi, Trakya Üniversitesi, Sağlık Bilimleri Enstitüsü, Edirne, 71.
  • Limtrakul, P., Lipigorngoson, S., Namwong, O., Apisariyakul, A., Dunn, F.W. 1997. İnhibitory effect of dietary curcuminon skin carcinogenezis in mice. Cancer Letters, 116 (2), 197-213.
  • Loeb, L.A. and Preston, B.D. 1986. Mutagenesis by apurinic/apyrimidinic sites. Annual Review of Genetics, 20, 201-230.
  • Majithiya, J.B., Balaraman, R., Gridhar, R. and Yadav, M.R. 2005. Effect of bis[curcumino]oxovanadium complex on non-diabetic and streptozotocin-induced diabetic rats. Journal of Trace Elements in Medicine and Biology, 18 (3), 211-217.
  • Matalon, S.T., Ornoy, A. and Lishner, M. 2004. Review of the potential effects of three commonly used antineoplastic and immunosuppresive drugs (cyclophosphamide, azathioprine, doxorubicin on the embryo and placenta). Reproductive Toxicology, 18, 219-230.
  • Moriya, S., Miyazawa, K., Kawaguchi, T., Che, X.F., Tomoda, A. 2011. Involment of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2- aminophenoxazine-3-one in cancer cells. International Journal of Oncolology, 39 (4), 981-988
  • Morse, M.A. and Stoner, G.D. 1993. Cancer chemoprevention: principles and prospects. Carcinogenesis 14 (9), 1737-1746.
  • Pandya, U., Saini, M.K., Jin, G.F., Godley, B.F. and Awasthi, Y.C. 2000. Dietary curcumin prevents ocular toxicity of naphthalene in rats. Toxicology Letters, 115 (3), 195-204.
  • Pfaffl, M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR, Nucleic Acids Research, 29 (9), 2002-2007.
  • Priyadarsini, K.I. 1997. Free radical reactions of curcumin in membrane models. Free Radical Biology& Medicine, 23 (6), 838-843.
  • Reddy, A.C and Lokesh, B.R. 1994. Studies of inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Molecular and Cellular Biochemistry, 137 (1), 1- 8.
  • Saha, A., Kuzuhara, T., Echigo, N., Fujıı, A., Suganuma, M. and Fujiki, H. 2010. Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of “Growth Arrest and DNA Damage Inducible Genes 45 and 153”. Biological & Pharmaceutical Bulletin, 33, 1291-1299.
  • Sajithlal, G.B., Chtihra, P. and Chandrakasan, G. 1998. Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. Biochemical Pharmacology, 56 (12), 1607-1614.
  • Sreejayan, N. and Rao, M.N. 1996 Free radical scavenging activity of curcuminoids. Arzneimittelforschung, 46 (2), 169-171.
  • Srivastava, R.K., Chen, Q., Siddiqui, I., Sarva, K., Shankar, S. 2007. Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21 (/WAF1/CIP1) Cell Cycl, 6 (23), 2953- 2961.
  • Singh, N.P., McCoy, M.T., Tice, R.R and Schneider, E.L. 1988. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research, 175 (1), 184-191.
  • Wattenberg, L.W. 1985. Chemoprevention of cancer. Cancer Research, 45 (1), 1-8.
  • Yener, Y. and Dikmenli, M. 2009. İncreased micronucleus frequency in rat bone marrow after acrylamide treatment. Journal of the Science of Food and Agriculture, 47, 2120-2123.
Year 2017, Volume: 17 Issue: 1, 18 - 27, 24.04.2017

Abstract

References

  • Abalea, V., Cillard, J., Dubos, M.P., Sergent, O., Cillard, P., Morel, I. 1999. Repair of iron-induced DNA oxidation by the flavonoid myricetin in primary rat hepatocyte cultures. Free Radical Biolology &Medicine, 26 (11-12), 1457-1466.
  • Agarwal, K.C. 1996. Therapeutic actions of garlic constituents. Medicinal Research Reviews, 16 (1), 111-124.
  • Aggarwal, B.B., Sethi, G., Ahn, K.S., Sandur, S.K., Pandey, M.K., Kunnumakkara, A.B., Sung, B. and Ichikawa, H. 2006. Targeting signal-transducer- and- activator-oftranscription- 3 for prevention and therapy of cancer: modern target but ancient solution. Annals of the New York Academy of the Sciences, 1091, 151-169.
  • Aggarwal, B.B., Gupta, S.C. and Sung, B. 2013a. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. British Journal of Pharmacology, 169 (8), 1672-1692.
  • Anand, P., Sundaram, C., Jhurani, S., Kunnumakkara, A.B. and Aggarwall, B.B. 2008. Curcumin and cancer: an “old-age “ disease with an “age-old” solution. Cancer Letters, 267 (1), 133-164.
  • Araŭjo, C.A. and Leon, L.L. 2001. Biological activities of Curcuma longa L. Memórıas do Instituto Oswaldo Cruz, 96 (5), 723-728.
  • Biswas, J., Roy, S., Mukherjee, S., Sinha, D. and Roy, M. 2010. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice. Asian Pasific Journal of Cancer Prevention, 11 (1), 239-247.
  • Boiteux, S. and Guillet, M. 2004. Abasic sites in DNA: repair and biological consequences in Saccharomyces cerevisae. DNA Repair, 3 (1), 1-12.
  • Cicchetti, R., Bari, M. and Argantin, G. 1999. Induction of micronuclei in bone marrow by two pesticides and their differentiation with CREST staining: an in vivo study in mice. Mutation Research, 439 (2), 239-248.
  • Corona, A., Urbina, P., Bobadilla, M., Vargas, J., Ramirez, M.A., Troyo, S., Diaz, P., Corona, J.R. 2007. Protective in vivo effect of curcumin on copper genotoxiciyt evaluated by comet and micronucleus assays. Journal of Applied Genetics, 48 (4), 389-396.
  • Cuce, G., Cetinkaya, S., İsitez, N., Kuccukturk, S., Sozen, M.E., Kalkan, S., Cigerci, İ.H. and Demirel, H.H. 2016. Effects of curcumin on methyl methanesulfonate damage to mouse kidney. Biotechnic & histochemistry, 91 (2), 122-127.
  • Franke, S.I., Pra D., Erdtmann, B., Henriques, J.A. and Silva, J. 2005. Influence of orange juice over the genotoxicity induced by alkylating agents: an in vivo analysis. Mutagenesis, 20 (4), 279-283.
  • Gopal, P., Paul, M. and Pau, S. 2014. Curcumin induces caspase mediated apoptosis in JURKAT cells by disrupting the redox balance. Asian Pacific Journal of Cancer Prevention, 15 (1), 93-100.
  • Horvathova, E., Slamenova, D., Hlincikova, L.,Mandal, T.K., Gabelova, A. and Collins, A.R. 1998. The nature and origin of DNA single-strand breaks determined with the comet assay. Mutation Research, 409, 163- 171.
  • Junk, N., Yi, Y.W., Kim, D., Shong, M., Hong, S.S., Lee, H.S. and Bae, I. 2000. Regulation of Gadd45γ expression by C/EBP. European Journal of Biochemistry, 267 (20), 6180-6187.
  • Kaufmann, L.T., Gierl, M.S., Niehrs, C. 2011. Gadd45a, Gadd45b and Gadd45g expression during mouse embryonic development. Gene Expression Patterns, 11 (8), 465-470.
  • Kunnumakkara, A.B., Bordoloi, D., Padmavathi, G., Monisha, J., Roy, N.K., Prasad, S. and Aggarwal, B.B. 2016. Curcumin, the golden nutraceutical: multitargeting for multiple chronic disease. British Journal of Pharmacology, doi: 10.1111/bph. 13621.
  • Kürkçü, E. 2008. Deneysel Olarak Oluşturulmuş Meme Tümörlerinde Curcumin’in Arginaz Enzim Aktivitesi, Ornitin ve Nitrik Oksit Düzeylerine Etkisi, Yüksek Lisans Tezi, Trakya Üniversitesi, Sağlık Bilimleri Enstitüsü, Edirne, 71.
  • Limtrakul, P., Lipigorngoson, S., Namwong, O., Apisariyakul, A., Dunn, F.W. 1997. İnhibitory effect of dietary curcuminon skin carcinogenezis in mice. Cancer Letters, 116 (2), 197-213.
  • Loeb, L.A. and Preston, B.D. 1986. Mutagenesis by apurinic/apyrimidinic sites. Annual Review of Genetics, 20, 201-230.
  • Majithiya, J.B., Balaraman, R., Gridhar, R. and Yadav, M.R. 2005. Effect of bis[curcumino]oxovanadium complex on non-diabetic and streptozotocin-induced diabetic rats. Journal of Trace Elements in Medicine and Biology, 18 (3), 211-217.
  • Matalon, S.T., Ornoy, A. and Lishner, M. 2004. Review of the potential effects of three commonly used antineoplastic and immunosuppresive drugs (cyclophosphamide, azathioprine, doxorubicin on the embryo and placenta). Reproductive Toxicology, 18, 219-230.
  • Moriya, S., Miyazawa, K., Kawaguchi, T., Che, X.F., Tomoda, A. 2011. Involment of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2- aminophenoxazine-3-one in cancer cells. International Journal of Oncolology, 39 (4), 981-988
  • Morse, M.A. and Stoner, G.D. 1993. Cancer chemoprevention: principles and prospects. Carcinogenesis 14 (9), 1737-1746.
  • Pandya, U., Saini, M.K., Jin, G.F., Godley, B.F. and Awasthi, Y.C. 2000. Dietary curcumin prevents ocular toxicity of naphthalene in rats. Toxicology Letters, 115 (3), 195-204.
  • Pfaffl, M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR, Nucleic Acids Research, 29 (9), 2002-2007.
  • Priyadarsini, K.I. 1997. Free radical reactions of curcumin in membrane models. Free Radical Biology& Medicine, 23 (6), 838-843.
  • Reddy, A.C and Lokesh, B.R. 1994. Studies of inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Molecular and Cellular Biochemistry, 137 (1), 1- 8.
  • Saha, A., Kuzuhara, T., Echigo, N., Fujıı, A., Suganuma, M. and Fujiki, H. 2010. Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of “Growth Arrest and DNA Damage Inducible Genes 45 and 153”. Biological & Pharmaceutical Bulletin, 33, 1291-1299.
  • Sajithlal, G.B., Chtihra, P. and Chandrakasan, G. 1998. Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. Biochemical Pharmacology, 56 (12), 1607-1614.
  • Sreejayan, N. and Rao, M.N. 1996 Free radical scavenging activity of curcuminoids. Arzneimittelforschung, 46 (2), 169-171.
  • Srivastava, R.K., Chen, Q., Siddiqui, I., Sarva, K., Shankar, S. 2007. Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21 (/WAF1/CIP1) Cell Cycl, 6 (23), 2953- 2961.
  • Singh, N.P., McCoy, M.T., Tice, R.R and Schneider, E.L. 1988. A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research, 175 (1), 184-191.
  • Wattenberg, L.W. 1985. Chemoprevention of cancer. Cancer Research, 45 (1), 1-8.
  • Yener, Y. and Dikmenli, M. 2009. İncreased micronucleus frequency in rat bone marrow after acrylamide treatment. Journal of the Science of Food and Agriculture, 47, 2120-2123.
There are 35 citations in total.

Details

Primary Language English
Journal Section Articles
Authors

Nilay İşitez This is me

İbrahim Hakkı Ciğerci This is me

Publication Date April 24, 2017
Submission Date September 8, 2016
Published in Issue Year 2017 Volume: 17 Issue: 1

Cite

APA İşitez, N., & Ciğerci, İ. H. (2017). Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 17(1), 18-27.
AMA İşitez N, Ciğerci İH. Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. April 2017;17(1):18-27.
Chicago İşitez, Nilay, and İbrahim Hakkı Ciğerci. “Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 17, no. 1 (April 2017): 18-27.
EndNote İşitez N, Ciğerci İH (April 1, 2017) Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 17 1 18–27.
IEEE N. İşitez and İ. H. Ciğerci, “Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 17, no. 1, pp. 18–27, 2017.
ISNAD İşitez, Nilay - Ciğerci, İbrahim Hakkı. “Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 17/1 (April 2017), 18-27.
JAMA İşitez N, Ciğerci İH. Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2017;17:18–27.
MLA İşitez, Nilay and İbrahim Hakkı Ciğerci. “Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, vol. 17, no. 1, 2017, pp. 18-27.
Vancouver İşitez N, Ciğerci İH. Effect of Curcumin On the Genotoxicity Induced By Alkylating Agents. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2017;17(1):18-27.