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INHIBITION OF FRIED MEAT-INDUCED DNA DAMAGE: A DIETARY INTERVENTION STUDY IN HUMANS
SHAUGHNESSY, D., L. GANGAROSA, B. SCHLIEBE, D. M. DEMARINI, D. UMBACH, R. SANDLER, AND J. TAYLOR. INHIBITION OF FRIED MEAT-INDUCED DNA DAMAGE: A DIETARY INTERVENTION STUDY IN HUMANS. Presented at The 9th International Conference on Environmental Mutagens, and the 36th Annual Meeting of the Environmental Mutagen Society, San Francisco, CA, September 03 - 08, 2005.
Dietary exposures have been implicated as risk factors in colorectal cancer. Such agents may act by causing DNA damage or may be protective against DNA damage. The effects of dietary exposures in causing or preventing damage have not been assessed directly in colon tissues. In this pilot study, 16 healthy volunteers were enrolled in a 4-�week controlled feeding study. In the first phase, eight subjects were fed diets containing meat cooked at either low or high temperature for 2-week periods in a crossover design. In the second phase, the remaining eight subjects were fed either the high-temperature fried meat diet or a diet containing high-temperature fried meat along with the putative inhibitors cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a 2-week crossover design. The high-temperature fried meat had high levels of heterocyclic amines (HCAs), whereas low-temperature fried meat had undetectable HCA levels. In both phases of the study, blood was drawn, and rectal biopsies were obtained from subjects each week during study. The effects of the different diets on DNA damage in colonic epithelium and lymphocytes were assessed using the single cell gel electrophoresis (comet) assay, and changes in urine mutagenicity were evaluated in the Salmonella plate-incorporation assay. For 6 out of 8 subjects in the first phase of the study, tail moment values in the comet assay were higher in colon epithelium from patients on diets containing high-temperature fried meat compared to those consuming the low-temperature meat diet, although the overall difference between the low- and high-temperature meat diets was not statistically significant. Tail Moment values were significantly lower in 7/8 subjects consuming diets with inhibitors and high- temperature meat compared to diets containing fried meat alone (p < 0.001). Urine mutagenicity increased in 8/8 subjects consuming the high-temperature vs. the low-temperature meat diet. For subjects consuming the inhibitor diet, unconjugated urine mutagenicity decreased in 4/8 subjects and conjugated mutagenicity increased in 7/8 of these subjects. Results from this pilot study will be used in the design of a larger study.