İnsan ve rat karaciğer primer hücre kültürlerinde farklı N-nitroso bileşiklerinin DNA üzerindeki etkileri

Abstract

The eftects of dinerent N-nitroso compounds in primary cultures of human and rat hepatocytes on the DNA

Abstract

Ten earcinogenic N-nitroso eompounds were examined for DNA-damaging activity in prımary cultures of human
'1nd rat h,:patocytes. DNA fragmentation was mcasured hy the alkaline dution techniClue. and unscheduled Df\A synthesis was by
qu,ıntitatiıe mıtoradiography. Positive dose-related responses in the range of subtoxic eoncentrations indicated were obtained ın cclls
of hoth species with N.nitrosodiethylanııne (I 0-32 mM). :"J-nitrosodi-n-propylamine (ı .s-l O mM). N-nitrosomorpholine (i -3.2 mM).
N nıtroscpıperidine (1-3.2 mM). N-nitrosopyrrolidine (3.2-1 S mM). N-nitroso-N-methylurca (O.32-I.S mM). N-nitroso-i\ .ethylurea
(0.32-1.8 mM) and N-nitroso-f\hutylurea (O. i-0.32 mM). N-nitrosodi-n-hutylamine was practicaııy inactive at the maximal soluble
conccntr,.tion (I mM). The results obtained from human hepatoeytes were Clualitatively similar LO those of rat hepatoeytes. hut
staıistieaııy. imp0rlant differenees hetween the two speeies in the amounts of DNA damage and/or unseheduled DNA synthesis were
observed wiıh N-nitrosodimethylamine. f\-nitrosomorpholine, N-nitrosopiperidine. N-nitrosopyrrolidine and N-nitroso-f\.
huıylıırca. On the other hand, 4uantitative differences in the gcnotoxie effeets indueed hy 5 mM-N-nitrosüdimethylaınine in eultures
derived from 20 human donors and from 20 rat were greater than average eoınpounds. These results indieate thaı the rat hepatocyte
DNA repair assay is a valid lI1terspeeies diflen::nccs displayed hy this nitrosamine and hy other N-niıroso model for predicting the
genotoxi" potentıal of N-nitroso compounds in human hepatocytes. 

Keywords

• DNA damage
• human
• rat

References

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