Diet and Genetic Damage
Condition: Diet
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Other
Time perspective: Prospective
Keywords: Heterocyclic Aminos; Cruciferous Vegetables; Yogurt; Chlorophyllin; Comet Assay; Diet; Healthy Volunteer