Analysis of Ki-ras exon 2 gene mutations in 3-methylcholanthrene and butylated hydroxytoluene-ınduced rat lung tissues

Bir polisiklik aromatik hidrokarbon ve potansiyel karsinojenik ajan olan MCA, deneysel kanser çalışmalarında sıklıkla kullanılır. BHT, yiyeceklerin tazeliğini, besin değerini, tadını ve rengini sabit tutmak ve korumak için, antioksidan olarak yıllardan beri yaygın olarak kullanılmaktadır. Bu çalışmanın amacı akciğer kanser gelişiminde, MCA ve BHT’nin rolünü araştırmak; Ki-ras ekson 2 geninde herhangi bir mutasyona neden olup olmadığını tespit etmektir. Ratlar son enjeksiyondan 26 hafta sonra servikal dislokasyon ile öldürüldü ve akciğer dokuları çıkarıldı. Kontrol ve deney grubu ratların akciğer dokuları Ki-ras ekson 2 geni nokta mutasyonları için PCR tabanlı SSCP analiziyle incelendi. Sonuç olarak Ki-ras ekson 2 geninde hiçbir nokta mutasyonu görülmedi.

3-metilkolantren ve bütil hidroksitoluenle uyarılmış rat akciğer dokularında Ki-ras ekson 2 geni mutasyon analizi

3-Methylcholanthrene (MCA) is a polycyclic aromatic hydrocarbon and potent carcinogenic agent that is often used in experimental cancer studies. Butylated hydroxytoluene (BHT) has been widely used for many years as an antioxidant to preserve and stabilize the freshness, nutritional value, flavor, and color of foods. The aim of the present study was to investigate the role of the application of MCA and BHT in the development of lung cancer, and to detect any mutation in the Ki-ras gene exon 2. Rats were killed by cervical dislocation 26 weeks after the last BHT injection and lung tissues were surgically removed. Lung tissues of the control and experiment rat groups were examined for point mutations in the exon 2 of the Ki-ras by PCR based SSCP analysis. No point mutation was observed in the Ki-ras gene exon 2.

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  • 1. Gressani MK, Rollins LA, Kabler SL et al. Induction of mutations in ki-ras and Ink4a in liver tumors of mice exposed in utero to 3- methylcholanthrene. Carcinogenesis 19: 1045-1052, 1998.
  • 2. Gressani KM, Kabler SL, O’Sullivan MG et al. Strain-dependent lung tumor formation in mice transplacentally exposed to 3- methylcholanthrene and post-natally exposed to butylated hydroxytoluene. Carcinogenesis 20: 2159-165, 1999.
  • 3. O'Donnell EP, Zerbe LK, Dwyer-Nield LD et al. Quantitative analysis of early chemically-induced pulmonary lesions in mice of varying susceptibilities to lung tumorigenesis. Cancer Lett 241:197-202,2006.
  • 4. Ruddon RW. Cancer Biology. Oxford University Press. New York;1995.
  • 5. Chepelev LL, Beshara CS, MacLean PD et al. Polypyrroles as antioxidants: kinetic studies on reactions of bilirubin and biliverdin dimethyl esters and synthetic model compounds with peroxyl radicals in solution. Chemical calculations on selected typical structures. J Org Chem 71: 22-30, 2006.
  • 6. Wang X, Witschi H. Mutations of the ki-ras protooncogene in 3- methylcholantrene and urethan-induced and butylated hydroxytoluene-promoted lung tumors of strain A/J and swr mice. Cancer Lett 91: 33-39, 1995.
  • 7. Witschi HP. Promotion of lung tumors in mice. Environ Health Perspect 50: 267-273, 1983.
  • 8. Brown LM, Malkinson AM, Rannels D et al. Compensatory lung growth after partial pneumonectomy enhances lung tumorigenesis induced by 3-methylcholanthrene. Cancer Research. 59: 5089- 5092, 1999.
  • 9. Mcdonald F, Ford CHJ. Oncogenes and Tumor Suppressor Genes. BIOS Scientific Publishers Limited, Oxford; 1991.
  • 10. Cooper GM. The Cell. ASM Press, Washington, D.C.; 2000.
  • 11. Köktürk N, Kırışoğlu CE, Öztürk C. Akciğer kanseri moleküler biyolojisi. Solunum 5: 127-138, 2003.
  • 12. Watanabe H, Shimokado K, Asahara T et al. Analysis of the c-myc, k-ras and p53 genes in methylcholanthrene-induced mouse sarcomas. Jpn. J. Cancer Res 90: 40-47, 1999.
  • 13. Maddox C, Wang B, Kirby PA et al. Mutagenicity of 3- methylcholantherene, PCB3, and 4-OH-PCB3 in the lung of transgenic BigBlue® rats. Environ Toxicol Pharmacol 25: 260-266,2008.
  • 14. Ozdemir O, Bulut H, Korkmaz M et al. Increased cell proliferation and rmsp1 fragmentation in testicular tissue of rat induced by 5- aza-2'-deoxycytidine. Exp Toxic Pathol 52: 317-322, 2000.
  • 15. Yin JJ, Xia Q, Cherng SH et al. UVA photoirradiation of oxygenated benz[a]anthracene and 3-methylcholanthene generation of singlet oxygen and induction of lipid peroxidation. Int J Environ Res Public Health 5: 26-31, 2008.
  • 16. Kasai A, Hiramatsu N, Hayakawa K et al. Direct, continuous monitoring of air pollution by transgenic sensor mice responsive to halogenated and polycyclic aromatic hydrocarbons. Environ Health Perspect 116: 349-354, 2008.
  • 17. Miller MS, Gressani KM, Leone-Kabler S et al. Differential sensitivity to lung tumorigenesis following transplacental exposure of mice to polycyclic hydrocarbons, heterocyclic amines, and lung tumor promoters. Exp Lung Res 26: 709-730, 2000.
  • 18. Shahidi F. Antioxidants in food and food antioxidants. Nahrung 44: 158-163, 2000.
  • 19. Solak M, Bağcı H, Şengil AZ et al. Moleküler Genetik ve Rekombinant DNA Teknolojisi. Afyon Kocatepe Üniversitesi Eğitim Sağlık ve Bilimsel Araştırmalar Vakfı, Yayın No: 5, 132, Afyon,2000.
  • 20. Aksoy K, Kayrın L, Tuli A et al. Tanıda DNA Teknikleri Yaz Okulu V. 53, Adana, 11-15 Haziran 2001.
  • 21. Meier BW, Gomez JD, Kirichenko OV et al. Mechanistic basis for inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4- methylphenol-treated mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes. Chem Res Toxicol 20: 199-207,2007.
  • 22. Witschi HP, Morse CC. Cell kinetics in mouse lung following administration of carcinogenesis and butylated hydroxytoluene. Toxicology and Applied Pharmacology 78: 464-472, 1985.
  • 23. Wessner LL, Fan M, Schaeffer DO et al. Mouse lung tumors exhibit specific ki-ras mutations following transplacental exposure to 3- methylcholanthrene. Carcinogenesis 7: 1519-1526, 1996.
Turkish Journal of Biology-Cover
  • ISSN: 1300-0152
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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