THE ASSOCIATION OF THE CARCİNOGENİC EFFECT OF N-NİTROSO-N-METHYLUREA WİTH THE BLOOD PLASMA VİTAMIN E AND SELENİUM LEVELS İN RATS

Yıl 2005, Cilt: 31 Sayı: 2, 109 - 118, 15.03.2013

Ahmet Gülçubuk Tahsin Yeşildere

Öz

Abstract

Effects of vitamin E and Se on cancer induced by N-N'itroso-N-Methylurea. which is a chemical carcinogen were investigated in this study. The study was carried out with 50 female Wistar-AIbino rats. The animals were divided into five groups: Four experimental and 1 control (n: 10). The animals in groups 1 and II were daily given 3ppm/lt sodium sclcnit via drinking water starting 45 days prior to NMU injection, while groups II and IV were injected vitamin E intraperitoneally (i.p) three times a week. At the end of the 45-day-period blood samples were taken from each animal in individual group via tail veins and the experimental groups (1-4) were administrated 20 mg/kg of NMU intraperitoneally three times a week during the second 45-day-period. After this stage vitamin E and Se application was prolonged for ¡70 days (experimental stage totally lasted for 260 days). All animals were sacrificed at the end of the study after the blood samples were obtained. Histologically, tumourai mass development was obtained in one (10%), five (50%), two (20%) and two animals (20%) in groups I (Se+NMU). II (Se+Vit.E+NMU). Ill (Vit.E+NMU) and IV (NMU), respectively. In conclusion, the ratio of tumourai development in group I. which was slightly lower than in group I pointed out at least the partial effectiveness of Se on prevention of neoplastic development. On the other hand, vitamin E was demonstrated to be ineffective in the prophylaxis of tumourai development due to equal tumour incidences detected in groups III (Vit.E) and IV (Only NMU). The ratio of tumourai development in group II (Se+Vit.E) was detected to be significantly higher than the other groups. Serum Se and vit.E levels in the relevant group were demonstrated to be lower than in group I (despite the insignificance of the estimated value) and significantly higher (p<0.05) than in group III. respectively, which all together indicated the likelihood of the inductive role of high serum levels of vit.E in tumour development.

Key Words: Vitamin E, Selenium, N-Nitroso-N-Methylurea, Cancer, Rat

 

SIÇANLARDA N-NİTROSO-N-METHYLUREA'NIN KARSİNOJEN ETKİSİNİN KAN PLAZMASINDAKİ E VİTAMİNİ VE SELENYUM DÜZEYLERİYLE İLİŞKİSİ

 

Özet

Bu çalışmada kimyasal bir karsinojen olan N-Nitroso-N-Methylurea (NMU) ile oluşturulan kanserlerde E vitamini (Vit.E) ve selenyumun (Se) etkisi araştınldı.Çalışmada 50 adet VVistar-albino dişi sıçan kullanıldı. Hayvanlar dört deney ve bir kontrol grubu olmak üzere beş gruba ayrıldı (n=10). Bir ve ikinci gruplara NMU enjeksiyonundan 45 gün önce başlanarak içme sularına günlük 3ppm/lt sodyum selenit eklendi. İki ve üçüncü gruplara aynı süre içerisinde haftada üç kez Vit.E intraperitoneal (i.p) uygulandı. Belirtilen sürenin sonunda bütün gruplardaki hayvanların kuyruk venalanndan kan alındı ve deney gruplarına (1-4) 45 gün boyunca haftada üç kez 20mg/kg NMU i.p uygulandı. Bu uygulamanın bitiminden çalışmanın sonuna kadar 170 gün daha (toplam 260 gün) Vit.E ve Se uygulamasına devam edildi.

Çalışmanın sonunda hayvanlardan tekrar kan alındıktan sonra ötanazi edilerek nekropsileri yapıldı.Histopatolojik inceleme sonunda birinci grupta (Se+NMU) bir hayvanda (%10), ikinci grupta (Se+Vit.E+NMU) beş hayvanda (Çi-50), üçüncü (VİLE+NMU) ve dördüncü grupta (NMU) ikişer hayvanda {7c20) tümör oluşumu saptandı.

Sonuç olarak Sc verilen birinci gruptaki tümör oranının dördüncü gruba göre birazda olsa düşük çıkması Se'un tümör oluşumunu engellemede kısmen de olsa etkili olduğunu, Vit.E verilen üçüncü grup ile yalnızca NMU verilen dördüncü grupta tümör oranlarının eşit çıkması nedeniyle de Vit.E'nm tümör oluşumunu engellemede etkisiz olduğunu göstermektedir. Ancak Se+Vit.E verilen ikinci gruptaki tümör oranının diğer gruplardan belirgin olarak yüksek çıkması, aynca bu gruptaki serum Se düzeyinin istatistiksel olarak anlamlı olmamakla birlikte birinci gruba göre düşük, serum Vit.E düzeyinin ise üçüncü gruba göre belirgin olarak yüksek (p<0.05) çıkması nedeniyle, serumda yüksek düzeyde bulunan Vit.E'nin tümör oluşumunu provake edebileceğini düşündürmektedir.

Anahtar Kelimeler: E vitamini, Selenyum, N-Nitroso-N-Methylurea, Kanser, Sıçan

Anahtar Kelimeler

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Kaynakça

• Appel, M.J., Hoetmer, A.G., Woutersen, R.A.: Lack of inhibitory effects of fi-carotcne. vitamin C. vitamin E and selenium on development of ductular adenocarcinomas in exocrine pancreas of hamsters. Cancer Lett. 1996: 103:157-162
• Bergman, K., Slanina, P.: Effect of dietary selenium compounds on Benzo (a)-pyrene- induced forestomach tumours and whole-blood glutathione peroxidase activities in C3H mice. Anticancer Res 1986: 6: 785-790
• Cohen, L.A., Epstein, M., Saa-Pabon. V., Meschter, C , Zang. E.: Interactions Between 4- HPR and diet in NML'-induced mammary tumourigenesis. Nutr. Cancer. 1994: 21: 271-283
• Dizdaroglu, M.: Chemical Determination of free radical-induced damage to DNA. Free Radic. Biol. Med, 1991; 10: 225-242
• Dizdaroglu, M.: Chemistry of free radical demage to DNA and nucleoproteins. In: Halliwel B. Aruoma Ol, Horwood E. editors. DNA and Free Radicals. New York: Ellis Horwood. 1993; 19-39
• Gould, M.N., Haag, J.D., Kennan, W.S., Tanner, M.A., Elson, C.H.: A comparison of tocopherol and tocotrienol for the chemopreventif of chemically induced rat mammary tumours. Am. J. Clin. Nutr, 1991: 53: 1068-1070
• Hadjiolov, D., Grueva, D.: Effect on combined tigason and selenium treatment on colon carcinogenesis. J. Cancer Res. Clin. Oncol, 1986: 112: 285-286
• Hoekstra, W.G.: Biochemical function of selenium its relation to vitamin E. Fed. Proc, 1975:34: 2083-2089
• Horvarth, P.M., Ip, C : Synergistic effect of Vitamin E and Selenium in the chemoprevention of mammary carcinogenesis in rats. Cancer Res, I983;43: 5335-5341
• Hotchkiss, J.H., Cassens, R.G.: Nitrate, Nitrite, and Nitroso Compounds in Foods. Food
• Tcchnol. 1987; 127-136
• Ip, C : Selenium inhibition of chemical carcinogenesis. Fed. Proc. 1985: 44. (9): 2573-2578
• Ahmet GULCUBUK - Tahsin YESjLDERE
• Kumar, V,, Cotran. R.S., Robbms, L.S.iTcmel Patoloji. In: Qevikbas U., Ceviri editdrii. Istanbul: Nobel & Yuce yayinlan, 1994. s. 171- 215
• Lathia, D., Blum, A.: Studie Uber die rolle des vitamin E als Nitritscavenger und N- Nitrosaminc-inhibitor. Fat. Sci. Technol. 1991:93.(7)271-274
• Lei, D.N., Wang, L.Q., Ruebner, B.H., Ilsieh, D.P.H., Wu, B.F., Zhu, C.R., Du, M.J.: Effect of Selenium on Anatoxin Hcpatocarcinogcnesis in the Rat. Biomed. Environ. Sci. 1990; 3: 65-80.
• Luna, G.L.: Manual of Histologic Staining Methods of the Armed Forces Institute of Pathology. McGraw-Hill Book Company, 1968
• Madewwel, B.R.: Cancer Diagnosis. In:Theilcn H, Madewell BR, editors. Veterinary Cancer Medicine. Philadelphia: Lea& Febigcr.. 1987; p. 3-25
• Mangues, R., Kahn, J.M., Seidman, I., Pellicer, A.: An overexpressed N-ras prolo- oncogene cooperates with N-Methylnitrosurea in mouse mammary carcinogenesis. Cancer Res, 1994; 54: 6395-6401
• Mizoguchi, M., Naito, H., Kurata, Y., Shibata, M.A., Tsuda, II., Wild, C P . , Montesano, R., Fukushima, S.: Influence of eging on multi-organ carcinogenesis in rats induced by N- Methyl-N-nitrosurea. Jpn. J. Cancer Res. 1993; 84: L39-146
• Pazos, P., Lanari, C , Meiss, R., Charreau, E.H., Paspualini, C D . : Mammary carcinogenesis induced by N-methyl-N-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) in BALB/c mice. Breast Cancer Res. Treat. 1991; 20:133-138
• Perchellet, J.P., Abney, NX., Thomas, R.M., Guislain, Y.L., Perchcllet, E.M.: Effect of combined treatments with selenium, glutathione, and vitamin E on glutathione peroxidase activity, ornithine decarboxylase induction, and complete and multistage carcinogenesis in mouse skin. Cancer Res. 1987; 47: 477-485
• Salonen, J.T., Salonen, R., Lappetelainen, R., Maenpaa, P.H., Alfthan, G., Puska, P.: Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case control analysis of prospective data. Br. Med. J, 1985; 290:417-420
• Tamano, S., Fukushima, S., Shirai, T., Hirose, M., Ito, N.: Modification by a-tocopherol, propyl gallate and tertiary buthylhydroquinone of urinary bladder carcinogenesis in fisher 344 rats pretreated with N-Buthyl-N-(4-Hydroxbutyl)Nitrosamine. Cancer Lett. 1987; 35: 39-46.
• Temple, N.J., El-Khatib, S.M.: Cabbage and vitamin E: Their effect on colon tumour formation in mice. Cancer Lett. 1987; 35: 71-77
• Yan, L., Yee, J.A., Boylan, L.M., Spallholz, J.E.: Effect of selenium compounds and thiols on human mammary tumour cells. Biol. Trace Elem. Res. 1991:30:145-161