Dietary Compounds that Enhance DNA Repair and their Relevance to Cancer and Aging (pp. 99-113)
Authors: (Harris Bernstein, Cheray Crowley-Skillicorn and Carol Bernstein et al., Univ. of Arizona, USA)
Abstract: Investigation of dietary compounds that enhance DNA repair has been a largely
underdeveloped area of research. DNA damage is regarded as a major contributing factor
to cancer and aging. Unrepaired DNA damage in cells that duplicate can cause errors of
replication leading to mutation and ultimately to cancer. Unrepaired DNA damages can
also cause loss of gene expression, loss of cell function and cell death (apoptosis) leading
ultimately to aging. Genetic defects in numerous human genes encoding DNA repair
proteins substantially increase the risk of cancer or cause premature aging, thus
indicating the importance of DNA repair processes in preventing cancer and premature
aging. Recent studies have identified several dietary compounds that increase expression
of DNA repair genes, and in some cases these compounds appear to be associated with
reduced cancer incidence or increased longevity.
We have tested 19 potential chemopreventive compounds for their effect on expression
of several DNA repair proteins in a colon cell line. On the basis of these results we
focused on a group of compounds related to chlorogenic acid. Chlorogenic acid is found
in a variety of fruits and vegetables, and is particularly high in coffee. We found that
chlorogenic acid and two of its metabolites formed by the action of intestinal microbial
flora, m-coumaric acid and 3-(m-hydroxyphenyl)propionic acid, significantly increased
the expression of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). The
repair enzyme Pms2 (post-meiotic segregation 2) was also significantly increased by mcoumaric
acid and 3-(m-hydroxyphenyl)propionic acid, as well as by another metabolite
of chlorogenic acid, caffeic acid. Evidence suggests that PARP activity is associated with
increased longevity and cancer prevention, and that Pms2 activity is associated with
cancer prevention. Thus, the increased expression of these DNA repair enzymes by
chlorogenic acid-related compounds may be beneficial for promoting longevity and
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