Mutagenesis vol. 18 no. 5 pp. 465-470,
September 2003
© 2003 UK Environmental Mutagen Society/Oxford University Press
,ß-Unsaturated carbonyl compounds: induction of oxidative DNA damage in mammalian cells
Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserlautern, 67663 Kaiserslautern, Germany and 1Zentrallaboratorium Deutscher Apotheker Forschungs gGmbH, 65760 Eschborn, Germany
,ß-Unsaturated carbonyl compounds occur in food and other environmental media. Due to their reactivity with cellular nucleophiles (e.g. Michael adduct formation with DNA bases and with glutathione) they might represent a potential health risk. In this study, induction of oxidative DNA damage was investigated in mammalian cells, as a consequence of glutathione depletion induced by selected food relevant 2-alkenals, including E-(2)-hexenal (HEX), (2E,4E)-2,4-hexadienal (HEXDI) and (E)-2-cinnamaldehyde (CA) and the cyclic analogue 2-cyclohexen-1-one (CHX). Oxidative DNA breakage was monitored with the Comet assay, using treatment with formamidopyrimidine-DNA glycosylase (FPG). Total cellular glutathione (tGSH) was determined in a kinetic, photometric assay. After 1 h incubation of V79 cells with HEX (100 µM) and CHX (300 µM), HEXDI and CA (300 µM each), tGSH was depleted down to <20% of control (viability >85%). Under these conditions, FPG-sensitive sites were not observed; moderate direct DNA breakage, however, was detectable. During 3 h post-incubation (without test compound) distinct oxidative DNA breakage occurred in HEX- and CA-, but not in CHX- and HEXDI-pretreated cells. Direct DNA breakage was markedly diminished, most probably by repair processes, and tGSH concentrations were observed to increase again within 3 h post-treatment. The results give strong evidence for alkenal-mediated oxidative stress contributing to cytotoxic/genotoxic cell damage. The extent of oxidative stress appears to be influenced by structure-specific properties of the alkenals.
2To whom correspondence should be addressed. Tel: +49 631 205 2532; Fax: +49 631 205 3085; Email: janzo{at}rhrk.uni-kl.de
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