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AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST

Year 2011, Volume: 1 Issue: 1, 83 - 94, 09.02.2011

Abstract

In this study, three different 9-Substituted phenantrene derivatives that were synthesized to be
used as basic matter for drugs were tested for their mutagenic potency in strains TA 98 and TA 100 of
Salmonella typhimurium by using Ames test. Therefore, both strains were tested in the absence or
presence of S9 metabolic activation, for five different doses of each test substances in two paralel independent
experiments. In the absence of metabolic activation, while only one of the compounds were
causing frame-shift mutations, two of them were determined to induce base pair substitution mutations.
In the presence of metabolic activation, while two of the compounds were mutagenic for TA 98,
base pair substitution mutations were not detected for any of the substances. Each of the compounds
tested were found to be mutagenic for at least one strain in the presence or absence of S9.

References

  • Abenesi, T., Polani, S.L. ve Perticne, P. (1998). DNA strand methylation and sister chromatid exchanges in mammalian cells in vitro. Mutation Research 429, 239-248.
  • Ames, B.N. ve McCann, J. (1981). Validation of the Salmonella test: A reply to Rinkus and Legator. Cancer Research 41, 4191.
  • Anders, M.W. ve Dekont, W. (1994). Conjugation-dependent carcinogenicity and toxicity of foreign compounds. Advance in Pharmacology 27, 511-519.
  • Arınç, E. ve Şen, A. (1994). Effect of in vivo Benzo(a)pyrene treatment on liver microsomal mixed-function oxidase activities of Gilthead seabream (Spararus aurata). Comparative Biochemistry and Physiology 107, 405-414.
  • Bostrom, E., Engen, S. ve Eide, I. (1998). Mutagenicity testing of organic extracts of diesel exhaust particles after spiling with polycyclic aromotic hydrocarbons. Archives of Toxicology 72, 645-649.
  • Cariello, N.F. ve Piegorsch, W.W. (1996). The Ames test: The two-fold rule revisited, Mutation Research 369, 23-31.
  • Chary, M.V., Keerthysri, N.C., Vupallapati, S.V.N., Lingaiah, N. ve Kantevari, S. (2008). Tetrabutylammonium bromide (TBAB) in isopropanol: An efficient, novel, neutral and recyclable catalytic system for the synthesis of 2,4,5- trisubstituted imidazoles Catalysis Communications 9, 2013-2017.
  • DeMeo, M., Vanella, P., Bernardini, E., Lagett, M., Maldonado, L., Jentzer, O., Crozet, M.P. ve Dumenill, G. (1992). Evaluation of the mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives by the Ames test and the SOS chromotest. Environmental and Molecular Mutagenesis 19(2), 167-181.
  • Debnath, A.K., Compadre, R.L., Debnath, G., Shusterman, A.J. ve Hansch, G. (1991). Structure-activity relationship of mutagenic aromatic and heteroaromatic nitro compounds correlation with molecular orbital energies and hydrophobicity. Journal of Medicinal Chemistry 34, 786- 797.
  • Edenharder, R., Ortseifen, M., Koch, M. ve Wesp, H.F. (2000). Soil mutagens are airborne mutagens: Variation of mutagenic activities induced in Salmonella typhimurium TA 98 and TA 100 by organic extracts of agricultural and forest soils in depence on location and season. Mutation Research 472, 23-36.
  • Glatt, H., Abu-Shqara, E., Harvey, R.G. ve Blum, J. (1994). Mutagenicity of Kregion oxides and imines of chrysene, benzo[c]phenantrene and benzo[g] chrysene in Salmonella typhimurium. Mutation Research 308, 135-141.
  • Glatt, H., Shtelzer, S., Sheradsky, T., Blum, J. ve Oesch, F. (1986). Mutagenicity of Nsubstituted phenantrene-9,10-imines in Salmonella typhimurium and chinese hamster V79 cells. Environmental Mutagenesis 8, 829-837.
  • Gu, Y.S., Kim, I.S., Ahn, J.K., Park, D.C., Yeum, D.M., Ji, C. ve Kim, S.B. (2002). Mutagenic and carcinogenic heterocyclic amines as affected by muscle types/skin and cooking in pan-roasted mackerel. Mutation Research. 515, 189-195.
  • Hamasaki, T., Sato, T., Nagase, H. ve Kito, H. (1992). The genotoxicity of organic compounds in SOS chromo test and rec-assay. Mutation Research 280, 195-203.
  • Hansch, C. (1991). Structure-activity relationships of chemical mutagens and carcinogens. The Science of the Total Environment 109, 17-29.
  • Hera, C. ve Pueyo, C. (1988). Response of the L-arabinose forward mutation assay of Salmonella typhimurium to frameshifttype mutagens. Mutation Research 203, 39-45.
  • Hirayama, T., Watanabe, T., Akita, M., Shimomura, S., Fujioka, Y., Ozasa, S. ve Fukui, O. (1988). Relationship between structure of nitrated arenes and their mutagenicity in Salomonella typhimurium; 2- and 2,7- nitro substitued fluorene, phenanthrene and pyrene. Mutation Research 209, 67- 74.
  • Işıkdağ, İ., Uçucu, Ü., Özdemir, A., Meriç, A., Öztürk, Y., Aydın, S. ve Ergun, B., “Synthesis and analgesıc actıvıtıes of 2- substituted-1H-phenantro[9,10- d]imidazoles” Boll.Chim.Farmaceutico 138 (1999) 453-456.
  • İ., Uçucu, Ü., Özdemir, A., Meriç, A., Öztürk, Y., Aydın, S. ve Ergun, B. (1999). Synthesis and analgesıc actıvıtıes of 2- substituted-1H-phenantro[9,10- d]imidazoles. Bolletino Chimico Farmaceutico 138, 453-456.
  • Jagdt, B., Warncke, K., Aver, H. ve Rudiger, H.W. (1996). Sleep deprivation does not induce sister chromatid exchange in humans. Mutation Research 361, 11-15.
  • Kasamatsu, T., Kohda, K. ve Kawazoa, Y. (1996). Comparison of chemically induced DNA breakage in cellular and subcellular systems using the comet assay. Mutation Research 369, 1-6.
  • Kato, T., Michikoshi, K., Minowa, Y. ve Kikugava, K. (2000). Mutagenicity of cooked hamburger is cotrolled delicated by reducing sugar content in ground beef. Mutation Research 471, 1-6.
  • Katsifis, S.D., Kinney, P.L., Hosselet, S., Burns, F.J. ve Christie, N.T. (1996). Interaction of nickel with mutagens in the induction of sister chromatid exchanges in human lymphocytes. Mutation Research 35, 7- 15.
  • Lawley, P.D. (1989). Mutagens as carcinogens: Devolopment of current concepts. Mutation Research 213, 3-25.
  • Lee, H., Bian, S.S. ve Chen, Y.L. (1994). Genotoxicity of 1,3-dithiane and 1,4- dithiane in the Cho/Sce assay and the Salmonella microsomal test. Mutation Research 312, 213-218.
  • Levin, D.E. ve Ames, B.N. (1986). Classifying mutagens as to their specifity in causing the six possitive transitions, transversions a simple analysis using the mutagenity assay. Environmental Mutagenesis 8, 9-28.
  • Lumbley, C.E., Parkinson, C. ve Walker, S.R. (1992). An International appraisal of the minumum duration of chronic animal toxicity studies. Human and Experimental Toxicology 11, 155- 162.
  • Maron, D.M. ve Ames, B.N. (1983). Revised methods for the Salmonella mutagenicity test. Mutation Research 113, 173-215
  • Meriç A., Incesu, Z. ve Isikdag, I. (2002). Synthesis and effects on intracellular calcium of some 1,3-bis-(heteroaryl subsstituted) benzene derivatives. Il Farmaco 57, 543- 548.
  • Nakamura, S., Oda, Y., Shimada, T., Ok, I. ve Sugimoto, K. (1987). SOS inducing activity of chemical carcinogens mutagens in S.L.TA. 1535/pSK 1002; examination with 151 chemicals. Mutation Research 192, 239-246.
  • Ridley, H.F., Spicket, R.G.W. ve Timmis, G.M. (1965). A new synthesis of benzimidazoles and aza-analogs. Journal of Heterocyclic Chemistry 2, 453-456.
  • Smith, C.J., Mc Karns, S.C., Davis, R.A., Livingston, S.D., Bombick, B.R., Avalos, J.T., Morgan, W.T. ve Doolittle, D.J. (1996). Human urine mutagenicity study comparing cigarettes which burn or primarily heat tobacco. Mutation Research 361, 1-9.
  • Vijayalaxami, R.R. ve Vetice, G.H.S. (1992). Assesment of radiotion induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis techniquei. Mutation Research 271, 243- 252.
  • Vrijsen, R., Michutte, Y. ve Bueye, A. (1990). Metabolic activation of quercetin mutagenecity, Mutation Research 232, 243-248.
  • Watanabe, T., Takashima, M., Kasai, T. ve Hirayama, T. (1997). Comparison of the mutational spesificity induced by environmental genoxin nitrated polycylic aromatic hydrocarbons in Salmonella typhimurium his genes. Mutation Research 394, 103-112.
  • Yapi, A.D., Mostafa, M., Valentin, A., Chavignon, O., Teulade, J.C., Mallie, M., Chapat, J.P. ve Blache, Y. (2000). New potential antimalerial agents; synthesis and biological activities of original diaza-analogs of phenantrene. Chemical Pharmaceutical Bulletin 48, 1886-1889.
  • Zsolnai, T. (1961). New fungicides. II. Nitro compounds. Biochemical Pharmacology 5, 304-387.

Yaşam Bilimleri ve Biyoteknoloji

Year 2011, Volume: 1 Issue: 1, 83 - 94, 09.02.2011

Abstract

Bu çalışmada, ilaç ön maddesi olarak sentezlenmiş olan üç farklı 9-Sübstitüye fenantren türevi, Ames test yöntemi kullanılarak, Salmonella typhimurium TA 98 ve TA 100 suşları yardımı ile mutajenik potansiyelleri açısından test edilmiştir. Bunun için, her iki suş, mikrozomal enzimler içeren metabolik aktivasyon (S9) varlığında ve yokluğunda, her bir test maddesinin beş ayrı dozu ile iki bağımsız deneyle araştırılmıştır. Metabolik aktivasyon yokluğunda, sentezlenen bileşiklerden yalnızca bir tanesi çerçeve kayması mutasyonlarına neden olurken, ikisinin baz çifti değişimi mutasyonlarını indüklediği belirlenmiştir. Metabolik aktivasyonlu ortamda ise iki madde TA 98 suşu için mutajen özellik gösterirken, baz çifti değişimi mutasyonu hiçbir madde için tespit edilmemiştir. Test edilen bileşiklerin her birinin, S9 varlığında veya yokluğunda, en az bir şuş için mutajenik özellikte olduğu tespit edilmiştir

References

  • Abenesi, T., Polani, S.L. ve Perticne, P. (1998). DNA strand methylation and sister chromatid exchanges in mammalian cells in vitro. Mutation Research 429, 239-248.
  • Ames, B.N. ve McCann, J. (1981). Validation of the Salmonella test: A reply to Rinkus and Legator. Cancer Research 41, 4191.
  • Anders, M.W. ve Dekont, W. (1994). Conjugation-dependent carcinogenicity and toxicity of foreign compounds. Advance in Pharmacology 27, 511-519.
  • Arınç, E. ve Şen, A. (1994). Effect of in vivo Benzo(a)pyrene treatment on liver microsomal mixed-function oxidase activities of Gilthead seabream (Spararus aurata). Comparative Biochemistry and Physiology 107, 405-414.
  • Bostrom, E., Engen, S. ve Eide, I. (1998). Mutagenicity testing of organic extracts of diesel exhaust particles after spiling with polycyclic aromotic hydrocarbons. Archives of Toxicology 72, 645-649.
  • Cariello, N.F. ve Piegorsch, W.W. (1996). The Ames test: The two-fold rule revisited, Mutation Research 369, 23-31.
  • Chary, M.V., Keerthysri, N.C., Vupallapati, S.V.N., Lingaiah, N. ve Kantevari, S. (2008). Tetrabutylammonium bromide (TBAB) in isopropanol: An efficient, novel, neutral and recyclable catalytic system for the synthesis of 2,4,5- trisubstituted imidazoles Catalysis Communications 9, 2013-2017.
  • DeMeo, M., Vanella, P., Bernardini, E., Lagett, M., Maldonado, L., Jentzer, O., Crozet, M.P. ve Dumenill, G. (1992). Evaluation of the mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives by the Ames test and the SOS chromotest. Environmental and Molecular Mutagenesis 19(2), 167-181.
  • Debnath, A.K., Compadre, R.L., Debnath, G., Shusterman, A.J. ve Hansch, G. (1991). Structure-activity relationship of mutagenic aromatic and heteroaromatic nitro compounds correlation with molecular orbital energies and hydrophobicity. Journal of Medicinal Chemistry 34, 786- 797.
  • Edenharder, R., Ortseifen, M., Koch, M. ve Wesp, H.F. (2000). Soil mutagens are airborne mutagens: Variation of mutagenic activities induced in Salmonella typhimurium TA 98 and TA 100 by organic extracts of agricultural and forest soils in depence on location and season. Mutation Research 472, 23-36.
  • Glatt, H., Abu-Shqara, E., Harvey, R.G. ve Blum, J. (1994). Mutagenicity of Kregion oxides and imines of chrysene, benzo[c]phenantrene and benzo[g] chrysene in Salmonella typhimurium. Mutation Research 308, 135-141.
  • Glatt, H., Shtelzer, S., Sheradsky, T., Blum, J. ve Oesch, F. (1986). Mutagenicity of Nsubstituted phenantrene-9,10-imines in Salmonella typhimurium and chinese hamster V79 cells. Environmental Mutagenesis 8, 829-837.
  • Gu, Y.S., Kim, I.S., Ahn, J.K., Park, D.C., Yeum, D.M., Ji, C. ve Kim, S.B. (2002). Mutagenic and carcinogenic heterocyclic amines as affected by muscle types/skin and cooking in pan-roasted mackerel. Mutation Research. 515, 189-195.
  • Hamasaki, T., Sato, T., Nagase, H. ve Kito, H. (1992). The genotoxicity of organic compounds in SOS chromo test and rec-assay. Mutation Research 280, 195-203.
  • Hansch, C. (1991). Structure-activity relationships of chemical mutagens and carcinogens. The Science of the Total Environment 109, 17-29.
  • Hera, C. ve Pueyo, C. (1988). Response of the L-arabinose forward mutation assay of Salmonella typhimurium to frameshifttype mutagens. Mutation Research 203, 39-45.
  • Hirayama, T., Watanabe, T., Akita, M., Shimomura, S., Fujioka, Y., Ozasa, S. ve Fukui, O. (1988). Relationship between structure of nitrated arenes and their mutagenicity in Salomonella typhimurium; 2- and 2,7- nitro substitued fluorene, phenanthrene and pyrene. Mutation Research 209, 67- 74.
  • Işıkdağ, İ., Uçucu, Ü., Özdemir, A., Meriç, A., Öztürk, Y., Aydın, S. ve Ergun, B., “Synthesis and analgesıc actıvıtıes of 2- substituted-1H-phenantro[9,10- d]imidazoles” Boll.Chim.Farmaceutico 138 (1999) 453-456.
  • İ., Uçucu, Ü., Özdemir, A., Meriç, A., Öztürk, Y., Aydın, S. ve Ergun, B. (1999). Synthesis and analgesıc actıvıtıes of 2- substituted-1H-phenantro[9,10- d]imidazoles. Bolletino Chimico Farmaceutico 138, 453-456.
  • Jagdt, B., Warncke, K., Aver, H. ve Rudiger, H.W. (1996). Sleep deprivation does not induce sister chromatid exchange in humans. Mutation Research 361, 11-15.
  • Kasamatsu, T., Kohda, K. ve Kawazoa, Y. (1996). Comparison of chemically induced DNA breakage in cellular and subcellular systems using the comet assay. Mutation Research 369, 1-6.
  • Kato, T., Michikoshi, K., Minowa, Y. ve Kikugava, K. (2000). Mutagenicity of cooked hamburger is cotrolled delicated by reducing sugar content in ground beef. Mutation Research 471, 1-6.
  • Katsifis, S.D., Kinney, P.L., Hosselet, S., Burns, F.J. ve Christie, N.T. (1996). Interaction of nickel with mutagens in the induction of sister chromatid exchanges in human lymphocytes. Mutation Research 35, 7- 15.
  • Lawley, P.D. (1989). Mutagens as carcinogens: Devolopment of current concepts. Mutation Research 213, 3-25.
  • Lee, H., Bian, S.S. ve Chen, Y.L. (1994). Genotoxicity of 1,3-dithiane and 1,4- dithiane in the Cho/Sce assay and the Salmonella microsomal test. Mutation Research 312, 213-218.
  • Levin, D.E. ve Ames, B.N. (1986). Classifying mutagens as to their specifity in causing the six possitive transitions, transversions a simple analysis using the mutagenity assay. Environmental Mutagenesis 8, 9-28.
  • Lumbley, C.E., Parkinson, C. ve Walker, S.R. (1992). An International appraisal of the minumum duration of chronic animal toxicity studies. Human and Experimental Toxicology 11, 155- 162.
  • Maron, D.M. ve Ames, B.N. (1983). Revised methods for the Salmonella mutagenicity test. Mutation Research 113, 173-215
  • Meriç A., Incesu, Z. ve Isikdag, I. (2002). Synthesis and effects on intracellular calcium of some 1,3-bis-(heteroaryl subsstituted) benzene derivatives. Il Farmaco 57, 543- 548.
  • Nakamura, S., Oda, Y., Shimada, T., Ok, I. ve Sugimoto, K. (1987). SOS inducing activity of chemical carcinogens mutagens in S.L.TA. 1535/pSK 1002; examination with 151 chemicals. Mutation Research 192, 239-246.
  • Ridley, H.F., Spicket, R.G.W. ve Timmis, G.M. (1965). A new synthesis of benzimidazoles and aza-analogs. Journal of Heterocyclic Chemistry 2, 453-456.
  • Smith, C.J., Mc Karns, S.C., Davis, R.A., Livingston, S.D., Bombick, B.R., Avalos, J.T., Morgan, W.T. ve Doolittle, D.J. (1996). Human urine mutagenicity study comparing cigarettes which burn or primarily heat tobacco. Mutation Research 361, 1-9.
  • Vijayalaxami, R.R. ve Vetice, G.H.S. (1992). Assesment of radiotion induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis techniquei. Mutation Research 271, 243- 252.
  • Vrijsen, R., Michutte, Y. ve Bueye, A. (1990). Metabolic activation of quercetin mutagenecity, Mutation Research 232, 243-248.
  • Watanabe, T., Takashima, M., Kasai, T. ve Hirayama, T. (1997). Comparison of the mutational spesificity induced by environmental genoxin nitrated polycylic aromatic hydrocarbons in Salmonella typhimurium his genes. Mutation Research 394, 103-112.
  • Yapi, A.D., Mostafa, M., Valentin, A., Chavignon, O., Teulade, J.C., Mallie, M., Chapat, J.P. ve Blache, Y. (2000). New potential antimalerial agents; synthesis and biological activities of original diaza-analogs of phenantrene. Chemical Pharmaceutical Bulletin 48, 1886-1889.
  • Zsolnai, T. (1961). New fungicides. II. Nitro compounds. Biochemical Pharmacology 5, 304-387.
There are 37 citations in total.

Details

Primary Language English
Journal Section Articles
Authors

Mehtap Kutlu

Esin Öztaş This is me

Gözde Aydoğan Kılıç

İlhan Işıkdağ This is me

Yusuf Özkay

Publication Date February 9, 2011
Published in Issue Year 2011 Volume: 1 Issue: 1

Cite

APA Kutlu, M., Öztaş, E., Aydoğan Kılıç, G., Işıkdağ, İ., et al. (2011). AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology, 1(1), 83-94.
AMA Kutlu M, Öztaş E, Aydoğan Kılıç G, Işıkdağ İ, Özkay Y. AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology. April 2011;1(1):83-94.
Chicago Kutlu, Mehtap, Esin Öztaş, Gözde Aydoğan Kılıç, İlhan Işıkdağ, and Yusuf Özkay. “AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST”. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology 1, no. 1 (April 2011): 83-94.
EndNote Kutlu M, Öztaş E, Aydoğan Kılıç G, Işıkdağ İ, Özkay Y (April 1, 2011) AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology 1 1 83–94.
IEEE M. Kutlu, E. Öztaş, G. Aydoğan Kılıç, İ. Işıkdağ, and Y. Özkay, “AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST”, Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology, vol. 1, no. 1, pp. 83–94, 2011.
ISNAD Kutlu, Mehtap et al. “AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST”. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology 1/1 (April 2011), 83-94.
JAMA Kutlu M, Öztaş E, Aydoğan Kılıç G, Işıkdağ İ, Özkay Y. AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology. 2011;1:83–94.
MLA Kutlu, Mehtap et al. “AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST”. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology, vol. 1, no. 1, 2011, pp. 83-94.
Vancouver Kutlu M, Öztaş E, Aydoğan Kılıç G, Işıkdağ İ, Özkay Y. AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST. Anadolu University Journal of Science and Technology C - Life Sciences and Biotechnology. 2011;1(1):83-94.