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Determinants of a genotoxic effect of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human diploid fibroblasts

✍ Scribed by Pohlmann, C. ;Koops, F. ;Berg, J. ;Holz, O. ;Ehlert, U. ;R�diger, H.W.

Publisher
Springer-Verlag
Year
1992
Tongue
English
Weight
362 KB
Volume
70-70
Category
Article
ISSN
1432-1440

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✦ Synopsis

The induction of micronuclei was studied in human diploid fibroblasts incubated in the presence of the tobacco-specific nitrosamine NNK. We used four fibroblast strains having a high capacity of O6-alkylguanine D N A alkyltransferase (13.0-23.3 pmol O6-methylguanine repaired per 8 × 10 6 cells) and four strains that showed no detectable repair capacity. Incubation with N N K doubled the frequency of micronuclei in repairdeficient cells but failed to evoke any effect in the proficient cell strains. Control experiments were performed with the direct methylating agent M N N G and in the presence of inhibitors of either metabolic activation or alkyltransferase. The results showed that the genotoxicity of N N K is dependent on the relationship between its metabolic activation and the constitutive DNA repair. This supports earlier findings that low constitutive levels of O6-alkylguanine D N A alkyltransferase may increase susceptibility to lung cancer after exposure to D N A methylating agents.

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