İnsan ve rat kararciğer primer hücre kültürlerinde farklı N-nitroso bileşiklerinin DNA üzerindeki etkileri
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Tarih
2002
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info:eu-repo/semantics/openAccess
Özet
On kanserojen N-nitroso bileşiği, insan ve rat karaciğer primer hücre kültürleri üzerinde DNA'ya hasar verici aktiviteleri açısından denendi; alkaline elüsyon tekniği kullanılarak DNA bölünmesi ve nicel otoradyografi kullanılarak da programlanmamış DNA sentezleri ölçüldü. Subtoksik konsantrasyonların aralığında pozitif dozla ilgili cevaplar her iki türün hücrelerinden 10-32 mM'lik N-nitrosodiethylamine, 1,8-10 mM'lik N-nitrosodi-n-propylamine, 1-3,2 mM'lik N-nitrosomorpholine, 1-3,2 mM'lik N-nitrosopiperidine, 3,2-18 mM'lik N-nitrosopyrrolidine, 0,32-1,8 mM'lik N-nitroso-N-methylurea, 0,32-1,8 mM'lik N-nitroso-N-ethylurea ve 0,1-0,32 mM'lik N-nitroso-N-butylurea kullanılarak elde edildi. N-nitrosodi-n-butylamine l mM'lik doymuş çözeltisi sabitti, insan karaciğer hücrelerinin tepkileri nitelik açısından rat karaciğer hücreleriyle benzerdi. Fakat istatistik açıdan, N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosopyrrolidine ve N-nitroso-N-butylurea kullanılarak gözlemlenen programlanmamış DNA sentezlerinde ve DNA hasar miktarlarında iki tür arasında önemli farklılıklar görüldü. Diğer taraftan, 20 insan ve 20 rat donöründen alınan kültürlerde 5 mM'lik N-nitrosodimethylamine ile uyarılmış genotoksik etkilerdeki miktarsal farklılıklar bu nitrosamine ve diğer N-nitroso bileşikleriyle ortaya çıkarılan ortalama türler arası farklılıklardan daha büyüktü. Rat hepatositlerindeki DNA onarım duyarlılığını işaret eden bu sonuçlar, insan hepatositlerindeki N-nitroso bileşiklerinin genotoksik potansiyelini tahmin etmek için geçerli bir model olduğunu gösterdi.
Ten carcinogenic N-nitroso compounds were examined for DNA-damaging activity in primary cultures of human and rat hepatocytes. DNA fragmentation was measured by the alkaline elution technique, and unscheduled DNA synthesis was by quantitative autoradiography. Positive dose-related responses in the range of subtoxic concentrations indicated were obtained'in cells of both species with N-nitrosodiethylamine (10-32 mM), N-nitrosodi-n-propylamine (1.8-10 mM), N-nitrosomorpholine.(l-3.2 mM), N-nitrosopiperidine (1-3.2 mM), N-nitrosopyrrolidine (3.2-18 mM), N-nitroso-N-methylurea (0.32-1.8 mM), N-nitroso-N-ethylurea (0.32-1.8 mM) and N-nitroso-N-butylurea (0.1-0.32 mM). N-nitrosodi-n-butylamine was practically'inactive at the maximal soluble concentration (1 mM). The results obtained from human hepatocytes were qualitatively similar to those of rat hepatocytes, but statistically, important differences between the two species in the amounts of DNA damage and/or unscheduled DNA synthesis were observed with N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosopyrrolidine and N-nitroso-N-butylurea. On the other hand, quantitative differences in the genotoxic effects induced by 5 inM-N-nitrosodimethylamine in cultures derived from 20 human donors and from 20 rat were greater than average compounds. These results indicate that the rat hepatocyte DNA repair assay is a valid interspecies differences displayed by this nitrosamine and by other N-nitroso model for predicting the genotoxic potential of N-nitroso compounds in human hepatocytes.
Ten carcinogenic N-nitroso compounds were examined for DNA-damaging activity in primary cultures of human and rat hepatocytes. DNA fragmentation was measured by the alkaline elution technique, and unscheduled DNA synthesis was by quantitative autoradiography. Positive dose-related responses in the range of subtoxic concentrations indicated were obtained'in cells of both species with N-nitrosodiethylamine (10-32 mM), N-nitrosodi-n-propylamine (1.8-10 mM), N-nitrosomorpholine.(l-3.2 mM), N-nitrosopiperidine (1-3.2 mM), N-nitrosopyrrolidine (3.2-18 mM), N-nitroso-N-methylurea (0.32-1.8 mM), N-nitroso-N-ethylurea (0.32-1.8 mM) and N-nitroso-N-butylurea (0.1-0.32 mM). N-nitrosodi-n-butylamine was practically'inactive at the maximal soluble concentration (1 mM). The results obtained from human hepatocytes were qualitatively similar to those of rat hepatocytes, but statistically, important differences between the two species in the amounts of DNA damage and/or unscheduled DNA synthesis were observed with N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosopyrrolidine and N-nitroso-N-butylurea. On the other hand, quantitative differences in the genotoxic effects induced by 5 inM-N-nitrosodimethylamine in cultures derived from 20 human donors and from 20 rat were greater than average compounds. These results indicate that the rat hepatocyte DNA repair assay is a valid interspecies differences displayed by this nitrosamine and by other N-nitroso model for predicting the genotoxic potential of N-nitroso compounds in human hepatocytes.
Açıklama
Anahtar Kelimeler
Veterinerlik
Kaynak
Ankara Üniversitesi Veteriner Fakültesi Dergisi
WoS Q Değeri
Scopus Q Değeri
Cilt
49
Sayı
1
