The consumption of foods prepared at high temperatures
has been
associated with numerous health risks. To date, the chief identified
source of risk has been small molecules produced in trace levels by
cooking and reacting with healthy DNA upon consumption. Here, we considered
whether the DNA in food itself also presents a hazard. We hypothesize
that high-temperature cooking may cause significant damage to the
DNA in food, and this damage might find its way into cellular DNA
by metabolic salvage. We tested cooked and raw foods and found high
levels of hydrolytic and oxidative damage to all four DNA bases upon
cooking. Exposing cultured cells to damaged 2′-deoxynucleosides
(particularly pyrimidines) resulted in elevated DNA damage and repair
responses in the cells. Feeding a deaminated 2′-deoxynucleoside
(2′-deoxyuridine), and DNA containing it, to mice resulted
in substantial uptake into intestinal genomic DNA and promoted double-strand
chromosomal breaks there. The results suggest the possibility of a
previously unrecognized pathway whereby high-temperature cooking may
contribute to genetic risks.