Increased mutagenicity of N-nitrosodiethanolamine in human lymphocyte cultures after activation by alcohol dehydrogenase.
The effect of alcohol dehydrogenase (ADH/NAD) from yeast and horse liver was tested on the induction of chromosomal mutations and sister chromatid exchanges (SCE) by N-nitrosodiethanolamine (NDELA) in human lymphocyte cultures. BrdUrd (27 micrograms) was added 24 h after starting the cultures to allow visualisation of SCE. ADH/NAD and NDELA were added 24 h later in different concentrations. No significantly higher level of numerical or structural chromosome aberrations was observed. However, the SCE frequency per cell was significantly increased by adding NAD (31.25 mumol and 62.5 mumol). The exclusive addition of 220 units ADH from yeast as well as 1.8 units ADH from horse liver also raised the number of SCE highly significantly. The combination of NAD and ADH was more effective than each substances alone in the yeast but not in the horse liver system. NDELA in a range of 12.5-62.5 mumol, given to cultures with ADH/NAD from yeast, additionally increased the SCE frequencies in a dose-dependent way. Similar results were found in cultures containing ADH/NAD from horse liver and 6.25-31.25 mumol NDELA, but the total numbers of SCE were distinctly higher. These results indicate that NDELA is strongly activated by ADH from yeast but even more by ADH from horse liver.
Henn
I
I
Department of Human Biology and Human Genetics, University of Kaiserslautern, Federal Republic of Germany.
Eisenbrand
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G
Zankl
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H
D000426:Alcohol Dehydrogenase / Q000494:pharmacology*; D001711:Biotransformation; D002478:Cells, Cultured; D004052:Diethylnitrosamine / Q000378:metabolism / Q000633:toxicity / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D009153:Mutagens; D009243:NAD / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009153:Mutagens; D009243:NAD; C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D000426:Alcohol Dehydrogenase