The purpose of this proposal is to ascertain whether a relationship exists between plasma and tissue levels of fat-soluble micronutrients such as alpha-tocopherol and gamma-tocopherol and carotenoids such as beta- carotene, alpha-carotene, lycopene, alpha-and beta-cryptoxanthins, lutein, zeaxanthin and the more polar epoxycarotenoids, neoxanthin and violaxanthin. The rationale for looking at fat-soluble micronutrients is that, at least in the case of beta-carotene, and to a certain extent in the case of alpha-tocopherol, both epidemiological and animal experiments have led investigators to propose that these compounds might serve as dietary anticarcinogens. Over a dozen human intervention studies are now underway in which beta-carotene is being supplied as a supplement to normal diets. The epidemiological investigations have observed a lower risk of several types of cancer in individuals that eat foods rich in beta-carotene or have relatively high concentrations of beta-carotene in their blood. The strongest association in these studies has dealt with lung cancer. Two problems still remain to be addressed. 1. Do the plasma beta-carotene or alpha-tocopherol levels accurately reflect tissue stores or tissue levels? 2. Does the inverse relationship between certain types of tumors and beta- carotene levels apply only to beta-carotene, or do other plasma and tissue carotenoids show the same, a better, or a poorer relationship? Both of these questions will be addressed by this proposal. We plan on surveying plasma, red blood cell, platelet, adipose tissue, buccal mucosal cells, and normal and precancerous skin, with respect to the levels of tocopherols and carotenoids. Samples will be obtained from Dermatology Clinic patients, as well as from normal volunteers. The development of sensitive HPLC techniques allows us to reliably analyze relatively small samples of tissues. We will follow the subjects over the course of time to see if there are time-dependent variations in any of the tissue pools of these micronutrients.
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