In Vitro And In Vivo Conditions Research Of Cyclophosphamide Mutagenicity And Zinc Interaction By Umu Test System Using Rat Urine Samples
Abstract
Keywords
References
- Ben-Yehuda, D., Krichevsky, S. and Caspi, O., 1996, Microsatellite Instability and p53 Mutations In Therapy Related Leuemia Suggest Mutator Phenotype. Blood, 88, 4296-4303.
- Bernacki, RJ., Bansl, SH. and Gurtoo, HL., 1987, Combinations of Mesna With Cyclophosphamide Adriamycine In Treatment of Mice With Tumors, Cancer Research 47, 799-802 .
- Bramwell, VCH., Mouridsen, HT., Santaro, A., Blackledge, G., Somers, R., Verwey, J., Dombernowsky, P., Onsrud, M., Thomas, D. and Sylvester, R., 1987, Cyclophosphamide Versus Ifosfamide, Final Report of A Randomized Phase II Trial In Adult Soft Tissue Sarcomas, Eur. J. Cancer Clin. Oncol., 311-321.
- Brock, N., Burkert, H., Günther, U., Hoefer-Janker, H., Metrenga, D., Schnitker, J. and Voigtman, R.,1979, Controlled Clinical Studies with an Antidote Against the Urotoxicity of Oxazaphosphorines: Preliminary Results, Cancer Treat. Rep., 63, 501-505.
- Ceyhan, E., 2001, 2,3-Difenil Substitue Kinoksalin’in 11 Farklı Türevinin Araştırılması,Yüksek Lisans Tezi. Aktivitesinin Umu Test Sistemi İle
- Ciliv, G., Emerk, B.ve Karan, A., 1980, İnsan Biyokimyasına Giriş, 224.
- Doğan, S., 2003, Antikanser Tedavide Siklofosfamid Nedenli Hemotoksisitenin Önlenmesinde Çinkonun Olası Sitoprotektif Etkileri, T.C. Osmangazi Üniversitesi Fen Bilimleri Enstitüsü Yüksek Lisans Tezi Biyoloji Anabilim Dalı.
- Gültekin, G., 2004, In Vivo ve In Vitro Şartlarda Cyclophosphamide Mutajenitesi ile Verapamil Etkileşiminin Rat İdrarında Umu Test Aracılığı ile Belirlenmesi, Osmangazi Üniversitesi Genel Biyoloji Bilim Dalı Yüksek Lisans Tezi.
- Kayaalp, O.,1989, Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, Feryal Kayaalp, O.,1991,Tıbbi Farmakoloji Altıncı Baskı,305-309.
- Kawabata, T.T., Chapman, M.Y., Kim, D.H., Stevens, W.D. and Holsapple, M.P., 1990. Mechanism of In Vitro Immunosuppression by Hepatocyte Hydroxicyclophosphamide, Biochemical Pharmacology., Vol.40, No. 5, 927-935.
- Cyclophosphamide Metabolites and 4
- Krupp, MA., Chatton, MJ. and Tierney, LM.,1986, Current Medical Diagnosis and Treatment Large Med. Pub., Copyright, 802-803.
- Lahdetie, J., Rety, R., and Sorsa, M., 1990, Interaction of Mesna With the Mutagenicity of Cyclophosphamide In Vitro and In Vivo Mutation Research, 245, 27-32.
- Lerza, R.,1988, Studies On Hemotoxicity of Cyclophosphamide, Doxorubicin and Cis-Diamminodichloroplatinum Combined With Sodium–2-Mercaptoethane Sulfonate, Tumori, 74, 333-337.
- Matsui, N., Kaya, T., Nagamine, K., Yasukawa, T., Shiku, H., Matsue, T., 2006, Electrochemical mutagen screening microbial chip, Biosensors & Bioelectronics 21 (7) 1202-1209.
- Miller, JH., 1972, Experiments in Molecular Genetics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 352-355.
- Moore, FR., Urda, GA., Krishna, G. and Theiss, JC., 1995, An In Vivo/In Vitro Method for Assessing Micronucleus and Chromosome Aberration Induction in Rat Bone Marrow and Spleen , Studies with Cyclophosphamide Mutat. Res. 335(2), 191-199.
- Oda, Y.,Yamazaki, H., Watanabe, M., Nohmi,T. and Shimada , T.,1993, Highly Sensitive Umu Test System For The Detection of Mutagenic Nitroarenes In Salmonella typhimurium NM 3009 Having High O- acetyltransferase and Nitroreductase Activities Environ and Molecular Mutagenesis, 21,357-364.
- Plaza, G., Nalecz-Jawecki, G., Ulfig, K., Brigmon, RL., 2005, Assessment of genotoxic activity of petrolium hydrocarbon- bioremediated soil, Ecotoxicology and Environmental Safety, 62, (3) 415-420.
- Pool, B.L., Bos, R.P., Niemeyer, U., Theuws, J.L.G. and Schmahl, D., 1988, In Vitro/ In Vivo Effect of Mesna on The Genotoxicity and Toxicty of Cyclophosphamide, A study Aimed At Clarifying The Mechanism of Mesna’s Anticarcinogenic Activity, Toxicology Letters, 41, 49-56.
- Povirk, L. and Shuker, D., 1994, DNA Damage and Mutagenesis Indeced by Nitrogen Mustards. Mutat. Res., 318, 205-226.
- Roosen, N., Doz, F.,Yeomans, KL., Dougherty, DV. and Rosenblum, ML.,1994, Effect of Pharmacologic Doses of Zinc On The Therapeutic Index of Brain Tumor Chemotheraphy With Carmustine,Cancer Chemotheraphy Pharmacology, 385-392.
- Scheef, W., Klein, HO., Moore, F.R., Urda, GA., Krishna, G. and Theiss, JC., 1995, An In Vivo/In Vitro Method for Assessing Micronucleus and Chromosome Aberration Induction in Rat Bone Marrow and Spleen , Studies with Cyclophosphamide Mutat. Res. 335(2), 191-199.
- Schmidt, B., Rasmussen, LH., Svendsen, GW., Ingerslev, F., Hansen, HCB., 2005, Genotoxic activity and inhibition of soil respiration by plaquibside a bracken fern carcinogen, Environmental Toxicology and Chemistry, 24 (1) 2751-2756.
- Wellinghausen, N., Kirchner, H. and Rink, L., 1997, The Immunobiology of Zinc. Immunology Today November vol. 18, 519- 521.
- Yenson, M.,1984, İnsan Biyokimyası 5. Baskı , Beta Basım Yayım
- Dağıtım A.Ş. İstanbul, 588-591.
- Le Bricon, T., Gugins, S., Cyoneber, L. and Baracos, V.E., 1995,
- Negative Impact of Cancer Chemoterapy on Protein Metabolsim in Healty and Tumor – Bearing Rats, Metabolism, 44(10):1340-1348
- Slattery, JI., Sanders, JE., Buckner, CD., Schaffer, RL., 1995, Graft – Rejection and Toxicity Following Bone Marrow Transplantation in Relation to Busulfan Pharmacocinetics, Bone Marrow Transolant, 16(1):31-42.
- Uchida, S., Suziki, K., Akıyama, S., Miyamoto, M., Juji, T. and Fujiwara, M., 1994, Suppressive Effect of Cyclophosphamide on the Progression of Lethal Graft-Versus-Host Disease in Mice: A Therapeutic Model of Fatal Post – Transfusion GVHD, Ther. Imuunol., 1(6):313- 318.
- Oda, Y., Nakamura, S., Oki, I., Kato, T. and Shinagausa, H., 1985, Evalution of the New System (Umu Test) For the Detection of Environmental Mutagens and Carcinogens, Mutation Res., 147:219-229.
İN VİVO VE İN VİTRO ŞARTLARDA CYCLOPHOSPHAMIDE MUTAJENİTESİ İLE ÇİNKO ETKİLEŞİMİNİN UMU TEST SİSTEMİ İLE RATLARIN İDRARLARINDA İNCELENMESİ
Abstract
Çalışmamızda ön tedavide sitotoksik ilaçlara karşı hücre direncini arttırmak
için iyi bir aday olduğu öne sürülen çinkonun 3000 μg/kg ve 6000 μg/kg
dozlarını kullanarak cyclophosphamide ‘in (CY) antineoplastik etkinliğini
düşürmeden toksisitesini azaltmayı ve daha yüksek dozlarda kullanılarak
daha güçlü bir terapotik etkinliğin sağlanması amaç edinildi
Bu deneysel çalışmada in vitro olarak ZnCl2’ün 3000 ve 6000 μg/kg dozları
ile CY’in 2500, 5000, 10000, 20000, 150000 μg/kg dozları ve bu dozlar
dahilindeki kombinasyonları Umu-test sistemi kullanılarak genotoksik ve
mutajenik değerlendirmeleri yapıldı.
Çalışmamızın ikinci aşamasında ise in vivo olarak 150000 μg/kg CY,
150000 μg/kg CY + 3000 μg/kg ZnCl2, 150000 μg/kg CY + 6000 μg/kg
ZnCl2 enjekte edilen sıçanlardan alınan idrar örnekleri yine umu test sistemi
ile değerlendirildi.
Umu test sistemi ile CY ve CY + ZnCl2 kombinasyonlarının ve yine idrar
örneklerinin bakteri test sistemleri ile verdikleri sonuçlar
genotoksik/mutajenik etki yaratmadığı gözlendi. Elde edilen deneysel
değerler kontrol olarak kullanılan 4NQO pozitif mutajen maddesinin
sonuçlarına yakın veya iki katı sonuçlar vermemiştir.
Sonuç olarak deneyde kullandığımız maddelerin genotoksik/mutajenik
etkileri bu uygulanan yönlendirilmiş mutasyon deneyleri ile cevap
vermemiştir.Ancak diğer kısa zamanlı ve uzun zamanlı testler ile değerlendirilmesi gerekmektedir. Çalışmalarımız bu doğrultuda devam
etmektedir.
Keywords
References
- Ben-Yehuda, D., Krichevsky, S. and Caspi, O., 1996, Microsatellite Instability and p53 Mutations In Therapy Related Leuemia Suggest Mutator Phenotype. Blood, 88, 4296-4303.
- Bernacki, RJ., Bansl, SH. and Gurtoo, HL., 1987, Combinations of Mesna With Cyclophosphamide Adriamycine In Treatment of Mice With Tumors, Cancer Research 47, 799-802 .
- Bramwell, VCH., Mouridsen, HT., Santaro, A., Blackledge, G., Somers, R., Verwey, J., Dombernowsky, P., Onsrud, M., Thomas, D. and Sylvester, R., 1987, Cyclophosphamide Versus Ifosfamide, Final Report of A Randomized Phase II Trial In Adult Soft Tissue Sarcomas, Eur. J. Cancer Clin. Oncol., 311-321.
- Brock, N., Burkert, H., Günther, U., Hoefer-Janker, H., Metrenga, D., Schnitker, J. and Voigtman, R.,1979, Controlled Clinical Studies with an Antidote Against the Urotoxicity of Oxazaphosphorines: Preliminary Results, Cancer Treat. Rep., 63, 501-505.
- Ceyhan, E., 2001, 2,3-Difenil Substitue Kinoksalin’in 11 Farklı Türevinin Araştırılması,Yüksek Lisans Tezi. Aktivitesinin Umu Test Sistemi İle
- Ciliv, G., Emerk, B.ve Karan, A., 1980, İnsan Biyokimyasına Giriş, 224.
- Doğan, S., 2003, Antikanser Tedavide Siklofosfamid Nedenli Hemotoksisitenin Önlenmesinde Çinkonun Olası Sitoprotektif Etkileri, T.C. Osmangazi Üniversitesi Fen Bilimleri Enstitüsü Yüksek Lisans Tezi Biyoloji Anabilim Dalı.
- Gültekin, G., 2004, In Vivo ve In Vitro Şartlarda Cyclophosphamide Mutajenitesi ile Verapamil Etkileşiminin Rat İdrarında Umu Test Aracılığı ile Belirlenmesi, Osmangazi Üniversitesi Genel Biyoloji Bilim Dalı Yüksek Lisans Tezi.
- Kayaalp, O.,1989, Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, Feryal Kayaalp, O.,1991,Tıbbi Farmakoloji Altıncı Baskı,305-309.
- Kawabata, T.T., Chapman, M.Y., Kim, D.H., Stevens, W.D. and Holsapple, M.P., 1990. Mechanism of In Vitro Immunosuppression by Hepatocyte Hydroxicyclophosphamide, Biochemical Pharmacology., Vol.40, No. 5, 927-935.
- Cyclophosphamide Metabolites and 4
- Krupp, MA., Chatton, MJ. and Tierney, LM.,1986, Current Medical Diagnosis and Treatment Large Med. Pub., Copyright, 802-803.
- Lahdetie, J., Rety, R., and Sorsa, M., 1990, Interaction of Mesna With the Mutagenicity of Cyclophosphamide In Vitro and In Vivo Mutation Research, 245, 27-32.
- Lerza, R.,1988, Studies On Hemotoxicity of Cyclophosphamide, Doxorubicin and Cis-Diamminodichloroplatinum Combined With Sodium–2-Mercaptoethane Sulfonate, Tumori, 74, 333-337.
- Matsui, N., Kaya, T., Nagamine, K., Yasukawa, T., Shiku, H., Matsue, T., 2006, Electrochemical mutagen screening microbial chip, Biosensors & Bioelectronics 21 (7) 1202-1209.
- Miller, JH., 1972, Experiments in Molecular Genetics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 352-355.
- Moore, FR., Urda, GA., Krishna, G. and Theiss, JC., 1995, An In Vivo/In Vitro Method for Assessing Micronucleus and Chromosome Aberration Induction in Rat Bone Marrow and Spleen , Studies with Cyclophosphamide Mutat. Res. 335(2), 191-199.
- Oda, Y.,Yamazaki, H., Watanabe, M., Nohmi,T. and Shimada , T.,1993, Highly Sensitive Umu Test System For The Detection of Mutagenic Nitroarenes In Salmonella typhimurium NM 3009 Having High O- acetyltransferase and Nitroreductase Activities Environ and Molecular Mutagenesis, 21,357-364.
- Plaza, G., Nalecz-Jawecki, G., Ulfig, K., Brigmon, RL., 2005, Assessment of genotoxic activity of petrolium hydrocarbon- bioremediated soil, Ecotoxicology and Environmental Safety, 62, (3) 415-420.
- Pool, B.L., Bos, R.P., Niemeyer, U., Theuws, J.L.G. and Schmahl, D., 1988, In Vitro/ In Vivo Effect of Mesna on The Genotoxicity and Toxicty of Cyclophosphamide, A study Aimed At Clarifying The Mechanism of Mesna’s Anticarcinogenic Activity, Toxicology Letters, 41, 49-56.
- Povirk, L. and Shuker, D., 1994, DNA Damage and Mutagenesis Indeced by Nitrogen Mustards. Mutat. Res., 318, 205-226.
- Roosen, N., Doz, F.,Yeomans, KL., Dougherty, DV. and Rosenblum, ML.,1994, Effect of Pharmacologic Doses of Zinc On The Therapeutic Index of Brain Tumor Chemotheraphy With Carmustine,Cancer Chemotheraphy Pharmacology, 385-392.
- Scheef, W., Klein, HO., Moore, F.R., Urda, GA., Krishna, G. and Theiss, JC., 1995, An In Vivo/In Vitro Method for Assessing Micronucleus and Chromosome Aberration Induction in Rat Bone Marrow and Spleen , Studies with Cyclophosphamide Mutat. Res. 335(2), 191-199.
- Schmidt, B., Rasmussen, LH., Svendsen, GW., Ingerslev, F., Hansen, HCB., 2005, Genotoxic activity and inhibition of soil respiration by plaquibside a bracken fern carcinogen, Environmental Toxicology and Chemistry, 24 (1) 2751-2756.
- Wellinghausen, N., Kirchner, H. and Rink, L., 1997, The Immunobiology of Zinc. Immunology Today November vol. 18, 519- 521.
- Yenson, M.,1984, İnsan Biyokimyası 5. Baskı , Beta Basım Yayım
- Dağıtım A.Ş. İstanbul, 588-591.
- Le Bricon, T., Gugins, S., Cyoneber, L. and Baracos, V.E., 1995,
- Negative Impact of Cancer Chemoterapy on Protein Metabolsim in Healty and Tumor – Bearing Rats, Metabolism, 44(10):1340-1348
- Slattery, JI., Sanders, JE., Buckner, CD., Schaffer, RL., 1995, Graft – Rejection and Toxicity Following Bone Marrow Transplantation in Relation to Busulfan Pharmacocinetics, Bone Marrow Transolant, 16(1):31-42.
- Uchida, S., Suziki, K., Akıyama, S., Miyamoto, M., Juji, T. and Fujiwara, M., 1994, Suppressive Effect of Cyclophosphamide on the Progression of Lethal Graft-Versus-Host Disease in Mice: A Therapeutic Model of Fatal Post – Transfusion GVHD, Ther. Imuunol., 1(6):313- 318.
- Oda, Y., Nakamura, S., Oki, I., Kato, T. and Shinagausa, H., 1985, Evalution of the New System (Umu Test) For the Detection of Environmental Mutagens and Carcinogens, Mutation Res., 147:219-229.
There are 32 citations in total.
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Articles |
| Authors | |
| Publication Date | June 1, 2008 |
| Submission Date | August 8, 2015 |
| Published in Issue | Year 2008 Volume: 8 Issue: 1 |