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ANTIMUTAGENICITY OF CINNAMALDEHYDE AND VANILLIN IN HUMAN CELLS: GLOBAL GENE EXPRESSION AND POSSIBLE ROLE OF DNA DAMAGE AND REPAIR
Citation:
KING, A. A., D. SHAUGHNESSY, K. MURE, W. O. WARD, D. M. UMBACH, Z. XU, D. DUCHARME, J. A. TAYLOR, D. M. DEMARINI, AND C. B. KLEIN. ANTIMUTAGENICITY OF CINNAMALDEHYDE AND VANILLIN IN HUMAN CELLS: GLOBAL GENE EXPRESSION AND POSSIBLE ROLE OF DNA DAMAGE AND REPAIR. MUTATION RESEARCH. Elsevier Science Ltd, New York, NY, 616(1-2):60-69, (2007).
Impact/Purpose:
To investigate the possibility that chemicals identified as antimutagens operate through a mechanism involving DNA damage.
Description:
This study investigated the possibility that chemicals identified as antimutagens may, in fact, operate through a mechanism involving DNA damage. We addressed this question by using two chemicals to which a large proportion of the population are exposed: vanillin and cinnemaldehyde. Both have been identified as antimutagens in bacterial systems, and we, in the present study, confirmed that they are antimutagens in mammalian (human) cells in culture at the HPRT locus. In addition, we showed that both induced DNA damage based on the comet assay, and we also showed through microarray analysis that both agents altered gene expression in genes involved in stress responses, oxidative damage, apoptosis, and cell growth. These results have identified a novel mechanism by which so-called ¿protective¿ agents, such as antimutagens, may, in fact, operate via a mechanism involving DNA damage. We propose that the DNA damage induced by such agents elicits a specific type of DNA repair (recombinational repair), which then reduces spontaneous mutation overall throughout the genome.
This study was done to explore the mechanism by which certain types of agents, which have been identified as antimutagens in microbial systems, are also antimutagens in human cells and to see what the mechanism is by which they work. People may be widely exposed to antimutagens in the diet, and such exposures may modify responses to environmental mutagens. An important question is how such agents may be protective to the genome and whether such agents are effective in human cells.
This study demonstrates that a certain class of compounds with wide-spread human exposure are antimutagenic in human cells, and that the mechanism involves the induction of DNA damage, which then elicits DNA repair¿resulting in an overall reduction in spontaneous mutation in the cells. Based on our previous studies, it appears that recombinational repair may be required for these agents to function as antimutagens rather than as mutagens. This highlights the importance of assessing the DNA repair background of individuals in molecular epidemiology studies involving genotoxic exposures. Given the polymorphic DNA repair background of the human population, determination of at least global DNA repair status would be informative when assessing risk for genotoxic exposures.