Diet and Genetic Damage

Overview

This study will examine the risks and protective effects of dietary factors on temporary genetic damage to cells lining the gastrointestinal tract and to blood cells. Some foods, including very well done meat, may increase genetic damage in cells, while others, such as yogurt and vegetables, may reduce genetic damage. This study may provide new information on the influence of diet on increasing or decreasing the risk of developing cancer, particularly colorectal cancer. The study is conducted at the General Clinical Research Center (GCRC) of the University of North Carolina. Nonsmoking, English-speaking, healthy adults between 18 and 45 years of age may be eligible for this 4-week study. Participants undergo the following tests and procedures: * Interview: Participants complete questionnaires including information on their diets, habits, past and present health, and family histories. * Diet: Participants adhere strictly to the diet provided by the dietician at the GCRC for all 4 weeks of the study. All meals are provided by the GCRC. All meals contain well-done meat and some contain yogurt, cruciferous vegetables, including broccoli and cabbage, and chlorophyllin tablets. Chlorophyllin is a compound in some foods that protects against genetic damage. * Urine sampling: Participants collect a urine sample each morning except Saturday and Sunday. * Stool sampling: Participants collect two stool samples during the study, one during the second week and another during the fourth week. * Blood draw: About 2-1/2 tablespoons of blood are drawn once a week for research purposes. The blood is tested for the effects of eating foods in the different diets used in the study. * Rectal biopsies: Four pinch biopsies, each about the size of a grain of rice, are taken from the rectum once a week for research purposes. For this procedure, forceps are inserted shallowly into the rectum to collect the tissue. The effects of the different diets on the colon cells are measured.

Colorectal cancer is one of the most common forms of cancer worldwide and is the second leading cause of cancer death in the United States. Given the frequency of occurrence and the poor prognosis for many afflicted individuals, prevention of this disease has been a major public health priority for the past few decades. However evidence from epidemiological studies has yet to explain the tremendous excess risk in developed countries, a trend that has been tentatively attributed to lifestyle and dietary factors. In the past few years, the consumption of red meat in particular, and other meat products, has attracted considerable attention in epidemiological, clinical, and experimental studies, with an increasing focus on a certain class of compounds found in cooked meat, heterocyclic amines. Heterocyclic amines are substances formed through pyrolysis of amino acids and creatine when meats are cooked at high temperature, particularly by pan-frying. Heterocyclic amine levels increase with cooking temperature, with the type and shape of the cooked piece of meat, with the degree of browning on the surface, and with the cooking method. In several epidemiological studies, including studies from Harvard, the International Agency for Research on Cancer (IARC), and the National Cancer Institute (NCI), individuals with long-term exposure to heterocyclic amines in their diet had an increased risk of colorectal cancers and colorectal adenomas, respectively. However, not all studies of heterocyclic amines in humans have shown a positive association with colorectal cancer risk, and clear consensus regarding this association is lacking. Based on the implications from these epidemiological studies, researchers at NCI have recently conducted a series of controlled feeding studies aimed at relating short-term exposure to heterocyclic amines through fried meat consumption to transient changes in urine mutagenicity levels. These studies provide evidence that meat fried at high temperatures results in significant short-term increases in exposure to mutagens. However, whereas urine mutagenicity appears to be a good short-term measure of exposure to heterocyclic amines in the diet, it is unclear as to whether these compounds induce genetic damage in colonic epithelial cells in humans. Against this background, we propose conducting a feeding study that includes the examination of colon tissue for evidence of transient DNA damage detected in the single cell gel electrophoresis (comet) assay following experimental intake of fried meat. This study will provide more direct evidence than previous studies as to whether genetic damage in colon epithelium and lymphocytes is related to dietary intake of heterocyclic amines. The use of the comet assay to detect the effects of diet on transient DNA damage is novel in this type of controlled feeding study, particularly with respect to monitoring effects of diet on colon epithelial cells. We will also monitor effects of fried meat ingestion on DNA damage in lymphocytes and detect changes in urinary mutagenicity related to these dietary regimens.