Diet and Genetic Damage

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.

• INCLUSION CRITERIA:

Nonsmoking, English speaking, healthy adults, ages 18-45 will be enrolled.

Exclusion criteria

Pregnant women will be excluded, as the dietary regimen in this study is not optimal for pregnant women.

Individuals will also be excluded if they consume more than two alcoholic drinks per day, have a history of illicit drug use, have a history of goiter, diabetes, colitis, or a diagnosed current thyroid condition, are excessively obese (BMI greater than 30), are vegetarians, or are currently taking anti-coagulant medication.

Individuals on prescription medications or antibiotics will be excluded.

Consumption of tea, or use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or vitamin or herbal supplements by participants will also be prohibited during the study.

Alcohol consumption will be prohibited during the study.

Children will not be enrolled in the study.