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Protective effect of N-acetyl cysteine on radiation-induced DNA damage in rat bone marrow: a comparison with WR-2721

Year 2008, Volume: 23 Issue: 3, 120 - 125, 01.04.2008

Abstract

OBJECTIVES To evaluate the potential radioprotective effects of N-acetylcysteine (NAC) against genocytotoxicity. As representative of a clinically used radioprotector, the effect of WR-2721 was compared with that of NAC using chromosomal aberration (CA) and mitotic index (MI) in the irradiated rat's femoral bone marrow cells. METHODS The rats (n=48) were divided randomly and equally into six groups as: Control (C), NAC (received 1000 mg/kg NAC), WR-2721 (200 mg/kg WR-2721), Radiation (R, received irradiation), R + NAC (received irradiation and 1000 mg/kg NAC), and R + WR-2721 (received irradiation and 200 mg/kg WR-2721). All the irradiated groups received whole-body gamma irradiation as a single dose of 6 Gy. At 72th hours, the rats were sacrificed and bone marrow cells were bilaterally collected from rats' femur. Then, cytogenetic and cytotoxicity tests were performed according to convantional methods. RESULTS Group R showed significantly higher CA and lower MI values when compared to C. R + NAC and R + WR-2721 groups showed significantly lower CA and higher MI averages when compared to R. CONCLUSION The results give clues about the beneficial effects of NAC against radiation-induced genocytotoxicity.

References

  • 1. Görpe A, Cantez S. Pratik nükleer t›p. ‹stanbul: ‹stanbul T›p Fakültesi Vakf›, Nobel Tip Kitabevi; 1992. s. 14-7.
  • 2. Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J 1987;1(6):441-5.
  • 3. Mc Clellan RO. The control of exposure of the public to ionizing radiation in the event of accident or attack. Biol effect of low-level rad 1983;288-301. 4. Macieira-Coelho A. Cancer and aging. Exp Gerontol 1986;21(6):483-95.
  • 5. Holmes GE, Bernstein C, Bernstein H. Oxidative and other DNA damages as the basis of aging: a review. Mutat Res 1992;275(3-6):305-15.
  • 6. Bohr VA, Dianov GL. Oxidative DNA damage processing in nuclear and mitochondrial DNA. Biochimie 1999;81(1-2):155-60.
  • 7. El-Habit OH, Saada HN, Azab KS, Abdel-Rahman M, El-Malah DF. The modifying effect of beta-carotene on gamma radiation-induced elevation of oxidative reactions and genotoxicity in male rats. Mutat Res 2000;466(2):179-86.
  • 8. Hui Z, Naikum Z, Rang Z, Xiumin L, Huifang C. Effect of ionizing radiation on bio-oxidase activities in cytoplasm of mouse blood liver cells. Chin J Radiol Med Prot 1996;16:179-82.
  • 9. Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 2001;27(3):247-54.
  • 10. Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003;111(15):1843-50.
  • 11. Lucas JN, Awa A, Straume T, Poggensee M, Kodama Y, Nakano M, et al. Rapid translocation frequency analysis in humans decades after exposure to ionizing radiation. Int J Radiat Biol 1992;62(1):53-63.
  • 12. Darroudi F, Natarajan AT, Bentvelzen AJ, Heidts PJ, Van Rotterdam A, Zoetelief J, et al. Detection of total and partial body irradiation in a mice model: a comparative study of chromosomal aberration, micronucleus and premature chromosome condensation assays. Int J Rad Biol 1992;74(2):207-15.
  • 13. Sener G, Kabasakal L, Atasoy BM, Erzik C, Velio¤luO¤ünç A, Cetinel S, et al. Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats. J Endocrinol 2006;189(2):257-69.
  • 14.Russell NS, Begg AC. Editorial radiotherapy and oncology 2002: predictive assays for normal tissue damage. Radiother Oncol 2002;64(2):125-9.
  • 15. Sy D, Hugot S, Savoye C, Ruiz S, Charlier M, Spotheim-Maurizot M. Radioprotection of DNA by spermine: a molecular modelling approach. Int J Radiat Biol 1999;75(8):953-61.
  • 16. Yuhas MJ, Philips TL. Parmacokinetics and mechanisms of action of WR-2721 and other protective agents. Radioprotector and Anticarciogenesis. New York: Academic Press; 1982. p. 639-53.
  • 17. Sölen G. Radioprotective effect of N-acetylcysteine in vitro using the induction of DNA breaks as end-point. Int J Radiat Biol 1993;64(4):359-66.
  • 18. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 2007;7(4):355-9.
  • 19. Prescott L. Oral or intravenous N-acetylcysteine for acetaminophen poisoning? Ann Emerg Med 2005;45(4):409-13.
  • 20. Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA. Highdose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci U S A 2006;103(12):4628-33.
  • 21. Nair CK, Parida DK, Nomura T. Radioprotectors in radiotherapy. J Radiat Res (Tokyo) 2001;42(1):21-37.
  • 22. Mansour HH, Hafez HF, Fahmy NM, Hanafi N. Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Biochem Pharmacol 2008;75(3):773-80.
  • 23. Neal R, Matthews RH, Lutz P, Ercal N. Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. Free Radic Biol Med 2003;34(6):689-95.

N-asetil-sistein'in sıçan kemik iliği hücrelerinde radyasyona bağlı DNA hasarından koruyucu etkisi ve WR-2721 ile karşılaştırması

Year 2008, Volume: 23 Issue: 3, 120 - 125, 01.04.2008

Abstract

AMAÇ Deneysel çalışmamızda radyasyonun biyolojik sistemlerde neden olduğu genotoksik etkilere karşı, N-asetil-sisteinin (NAS) koruyucu etkileri konvensiyonel sitogenetik yöntemlerle (kromozom aberasyonu-CA, mitotik indeks-MI) amifostinle (WR-2721) karşılaştırıldı. GEREÇ VE YÖNTEM Co-60 cihazı ile 6 Gy tek doz tüm vücudu ışınlanan sıçanların femur-kemik ilikleri incelendi. Kontrol (K); radyasyon (R); NAS; amifostin (WR-2721) R + NAS (R + NAS); R + WR-2721 gruplarında, eşit sayıda toplam 48 dişi sıçan kullanıldı. R grubu yalnız radyasyon, R + WR-2721 grubuna radyasyon öncesi WR-2721 (200 mg/kg, i.p.), R + NAS grubuna NAS (1000 mg/kg, i.p.) verildi; 72 saat sonra tüm grupların preperasyonu konvensiyonel sitogenetik yöntemlerle hazırlanarak incelendi. BULGULAR R grubunun ortalama CA değeri en yüksek, MI değeri düşük olup; kontrol grubuna göre bu fark anlamlıydı. R + NAS ve R + WR-2721 gruplarında R grubuna göre hasar göstergeleri daha düşüktü; farklar istatistiksel olarak anlamlıydı. SONUÇ Bu sonuçlara göre, iyonize radyasyonun erken dönemdeki genotoksik etkilerine karşı amifostin ve NAS'nin koruyucu etkilerinin benzer olduğunu söylenebilir

References

  • 1. Görpe A, Cantez S. Pratik nükleer t›p. ‹stanbul: ‹stanbul T›p Fakültesi Vakf›, Nobel Tip Kitabevi; 1992. s. 14-7.
  • 2. Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J 1987;1(6):441-5.
  • 3. Mc Clellan RO. The control of exposure of the public to ionizing radiation in the event of accident or attack. Biol effect of low-level rad 1983;288-301. 4. Macieira-Coelho A. Cancer and aging. Exp Gerontol 1986;21(6):483-95.
  • 5. Holmes GE, Bernstein C, Bernstein H. Oxidative and other DNA damages as the basis of aging: a review. Mutat Res 1992;275(3-6):305-15.
  • 6. Bohr VA, Dianov GL. Oxidative DNA damage processing in nuclear and mitochondrial DNA. Biochimie 1999;81(1-2):155-60.
  • 7. El-Habit OH, Saada HN, Azab KS, Abdel-Rahman M, El-Malah DF. The modifying effect of beta-carotene on gamma radiation-induced elevation of oxidative reactions and genotoxicity in male rats. Mutat Res 2000;466(2):179-86.
  • 8. Hui Z, Naikum Z, Rang Z, Xiumin L, Huifang C. Effect of ionizing radiation on bio-oxidase activities in cytoplasm of mouse blood liver cells. Chin J Radiol Med Prot 1996;16:179-82.
  • 9. Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 2001;27(3):247-54.
  • 10. Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003;111(15):1843-50.
  • 11. Lucas JN, Awa A, Straume T, Poggensee M, Kodama Y, Nakano M, et al. Rapid translocation frequency analysis in humans decades after exposure to ionizing radiation. Int J Radiat Biol 1992;62(1):53-63.
  • 12. Darroudi F, Natarajan AT, Bentvelzen AJ, Heidts PJ, Van Rotterdam A, Zoetelief J, et al. Detection of total and partial body irradiation in a mice model: a comparative study of chromosomal aberration, micronucleus and premature chromosome condensation assays. Int J Rad Biol 1992;74(2):207-15.
  • 13. Sener G, Kabasakal L, Atasoy BM, Erzik C, Velio¤luO¤ünç A, Cetinel S, et al. Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats. J Endocrinol 2006;189(2):257-69.
  • 14.Russell NS, Begg AC. Editorial radiotherapy and oncology 2002: predictive assays for normal tissue damage. Radiother Oncol 2002;64(2):125-9.
  • 15. Sy D, Hugot S, Savoye C, Ruiz S, Charlier M, Spotheim-Maurizot M. Radioprotection of DNA by spermine: a molecular modelling approach. Int J Radiat Biol 1999;75(8):953-61.
  • 16. Yuhas MJ, Philips TL. Parmacokinetics and mechanisms of action of WR-2721 and other protective agents. Radioprotector and Anticarciogenesis. New York: Academic Press; 1982. p. 639-53.
  • 17. Sölen G. Radioprotective effect of N-acetylcysteine in vitro using the induction of DNA breaks as end-point. Int J Radiat Biol 1993;64(4):359-66.
  • 18. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 2007;7(4):355-9.
  • 19. Prescott L. Oral or intravenous N-acetylcysteine for acetaminophen poisoning? Ann Emerg Med 2005;45(4):409-13.
  • 20. Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA. Highdose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci U S A 2006;103(12):4628-33.
  • 21. Nair CK, Parida DK, Nomura T. Radioprotectors in radiotherapy. J Radiat Res (Tokyo) 2001;42(1):21-37.
  • 22. Mansour HH, Hafez HF, Fahmy NM, Hanafi N. Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Biochem Pharmacol 2008;75(3):773-80.
  • 23. Neal R, Matthews RH, Lutz P, Ercal N. Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. Free Radic Biol Med 2003;34(6):689-95.
There are 22 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Can Demirel This is me

Sevil Kılçıksız This is me

Özlem İzci Ay This is me

Serkan Gürgül This is me

M. Ertan Ay This is me

Nurten Erdal This is me

Publication Date April 1, 2008
Published in Issue Year 2008 Volume: 23 Issue: 3

Cite

APA Demirel, C., Kılçıksız, S., Ay, Ö. İ., Gürgül, S., et al. (2008). N-asetil-sistein’in sıçan kemik iliği hücrelerinde radyasyona bağlı DNA hasarından koruyucu etkisi ve WR-2721 ile karşılaştırması. Türk Onkoloji Dergisi, 23(3), 120-125.
AMA Demirel C, Kılçıksız S, Ay Öİ, Gürgül S, Ay ME, Erdal N. N-asetil-sistein’in sıçan kemik iliği hücrelerinde radyasyona bağlı DNA hasarından koruyucu etkisi ve WR-2721 ile karşılaştırması. Türk Onkoloji Dergisi. April 2008;23(3):120-125.
Chicago Demirel, Can, Sevil Kılçıksız, Özlem İzci Ay, Serkan Gürgül, M. Ertan Ay, and Nurten Erdal. “N-Asetil-sistein’in sıçan Kemik iliği hücrelerinde Radyasyona bağlı DNA hasarından Koruyucu Etkisi Ve WR-2721 Ile karşılaştırması”. Türk Onkoloji Dergisi 23, no. 3 (April 2008): 120-25.
EndNote Demirel C, Kılçıksız S, Ay Öİ, Gürgül S, Ay ME, Erdal N (April 1, 2008) N-asetil-sistein’in sıçan kemik iliği hücrelerinde radyasyona bağlı DNA hasarından koruyucu etkisi ve WR-2721 ile karşılaştırması. Türk Onkoloji Dergisi 23 3 120–125.
IEEE C. Demirel, S. Kılçıksız, Ö. İ. Ay, S. Gürgül, M. E. Ay, and N. Erdal, “N-asetil-sistein’in sıçan kemik iliği hücrelerinde radyasyona bağlı DNA hasarından koruyucu etkisi ve WR-2721 ile karşılaştırması”, Türk Onkoloji Dergisi, vol. 23, no. 3, pp. 120–125, 2008.
ISNAD Demirel, Can et al. “N-Asetil-sistein’in sıçan Kemik iliği hücrelerinde Radyasyona bağlı DNA hasarından Koruyucu Etkisi Ve WR-2721 Ile karşılaştırması”. Türk Onkoloji Dergisi 23/3 (April 2008), 120-125.
JAMA Demirel C, Kılçıksız S, Ay Öİ, Gürgül S, Ay ME, Erdal N. N-asetil-sistein’in sıçan kemik iliği hücrelerinde radyasyona bağlı DNA hasarından koruyucu etkisi ve WR-2721 ile karşılaştırması. Türk Onkoloji Dergisi. 2008;23:120–125.
MLA Demirel, Can et al. “N-Asetil-sistein’in sıçan Kemik iliği hücrelerinde Radyasyona bağlı DNA hasarından Koruyucu Etkisi Ve WR-2721 Ile karşılaştırması”. Türk Onkoloji Dergisi, vol. 23, no. 3, 2008, pp. 120-5.
Vancouver Demirel C, Kılçıksız S, Ay Öİ, Gürgül S, Ay ME, Erdal N. N-asetil-sistein’in sıçan kemik iliği hücrelerinde radyasyona bağlı DNA hasarından koruyucu etkisi ve WR-2721 ile karşılaştırması. Türk Onkoloji Dergisi. 2008;23(3):120-5.