Summary
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 μg) 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 μmol and 62.5 μmol). 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 μmol, 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 μmol 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.
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Abbreviations
- NDELA:
-
N-nitrosodiethanolamine
- ADH:
-
alcohol dehydrogenase
- SCE:
-
sister chromatid exchange
References
Airoldi L, Macri A, Bonfati M, Bonati M, Fanelli R (1984) Kinetics and bioavailability of N-nitrosodiethanolamine after intravenous and cutaneous administration to rats. Food Chem Toxicol 22:133–138
Brunnemann KD, Hoffmann D (1981) Assessment of the carcinogenic N-nitrodiethanolamine in tobacco products and tobacco smoke. Carcinogenesis 2:1123–1127
Denkel E, Pool BL, Sterzel W, Eisenbrand C (1985) Biological activity of potential metabolites of N-nitrosodiethanolamine which may arise after activation by alcoholdehydrogenase 4th ICEM Stockholm, June 1985
Denkel E, Pool BL, Schlehofer IR, Eisenbrand G (1986) Biological activity of N-nitrosodiethanolamine and of potential metabolites which may arise after activation by alcohol dehydrogenase in Salmonella typhimurium, in mammalian cells, and in vivo. J Cancer Res Clin Oncol 111:149–153
Dittberner U, Eisenbrand G, Zankl H (1988) Cytogeneic effects of Nnitrosodiethanolamine (NDELA) and NDELA monoacetate in human lymphocytes. J Cancer Res Clin Oncol 114:575–578
Eisenbrand G, Sommer H (1989) A method for determination of N-nitrosoalkanolamines in cosmetics. Z Lebensm Unters Forsch (in press)
Eisenbrand G, Denkel E, Pool B (1984) Alcohol dehydrogenase as an acitvating enzyme for N-nitrosodiethanolamine (NDELA): in vitro activation of NDELA to a potent mutagen in Salmonella typhimurium. J Cancer Res Clin Oncol 108:76–80
Gilbert P, Fabry L, Rollmann B, Lombart P, Rondelet J, Poncelet F, Leonard A, Mercier M (1981) Mutagenicity of N-nitrosodiethanolamine and its acetyl derivatives. Mutat Res 89:217–228
Hecht SS (1984) N-Nitroso-2-hydroxymorpholine, a mutagenic metabolite of N-nitrosodiethanolamine. Carcinogenesis 5:1745–1747
Kerklaan P, Mohn C, Bouter S (1981) Comparison of the mutagenic activity of dialkylnitrosamines in animal-mediated and in vitro assays using an Escherichia coli indicator. Carcinogenesis 2:909–914
Lijinski W, Andrews AW (1983) The superiority of hamster liver microsomal fraction for activating nitrosamines to mutagens in Salmonella typhimurium. Mutat Res 111:135–144
Lijinsky W, Reuber MD, Mannig WB (1980) Potent Carcinogenicity of N-nitrosodiethanolamine in rats. Nature 288:589–590
Lijnsky W, Losikoff AM, Sansone EB (1981) Penetration of rat skin by N-nitrosodiethanolamine and N-nitrosomorpholine. J Natl Cancer Inst 66:125–127
Michejda CJ, Andrews AW, Koepke SR (1979) Derivates of sidechain hydroxylated nitrosamines direct acting mutagens in Salmonella typhimurium. Mutat Res 67:301–308
Perry P, Wolff S (1974) A new giemsa method for the differential staining of sister chromatids. Nature 251:156–158
Preussmann R, Habs M, Habs H, Schmähl D (1982) Carcinogenicity of N-nitrosodiethanolamine in rats at five different dose levels. Cancer Res 42:5167–5172
Spiegelhalder B, Preussmann R (1982) in: Bartsch H, O'Neill IK, Castegnaro R, Okada M (eds) N-nitroso compounds: occurrence and biological effects. IARC Scientific Publ 41:231–243
Spiegelhalder B, Preussmann R (1984) Contamination of toiletries and cosmetic products with volatile and nonvolatile N-nitroso carcinogens. J Cancer Res Clin Oncol 108:160–163
Spiegelhalder B, Hartung M, Preussmann R (1984) Biological monitoring in metal working industry. IARC Scientific Publ 57:943–946
Sterzel W, Eisenbrand G (1986) N-nitrosodiethanolamine is activated in the rat to an ultimate genotoxic metabolite by sulfotransferase. J Cancer Res Clin Oncol 111:20–24
Zingmark PA, Rappe C (1977) On the formation of N-nitrosodiethanolamine in a grinding fluid concentrate after storage. Ambio 6:237–238
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Henn, I., Eisenbrand, G. & Zank, H. Increased mutagenicity of N-nitrosodiethanolamine in human lymphocyte cultures after activation by alcohol dehydrogenase. J Cancer Res Clin Oncol 115, 445–448 (1989). https://doi.org/10.1007/BF00393334
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DOI: https://doi.org/10.1007/BF00393334