Because the relationships between dietary intake, blood levels and body stores are largely unknown, prediction of tissue levels or total body stores from blood levels may be inaccurate. We have already shown that liver vitamin A (which represents 90+% total body stores) can not be predicted from blood levels, but it can be predicted quite well from stable isotope dilution measurements in blood (Furr et al., (1989) Am. J. Clin. Nutr. 49:713-716, appended). Therefore we propose to use the stable isotope dilution approach in addition to direct measurements of vitamin A and beta-carotene in tissues to determine the extent to which isotope dilution measurements in blood predict tissue levels, total body stores, and dietary intake of these nutrients. Tissues will be obtained from surgical caseloads at he University of California Davis Medical Center (UCDMC) and Kaiser Permanente Hospital (a teaching hospital of UCDMC) Usual dietary intakes of vitamin A and beta-carotene will be measured (Block et al,. 1985) to evaluate the relationship of intake to tissue levels and the effect of intake on the relationship of blood to tissue levels. Normal blood and tissues and blood and tissues from patients with the three most common fatal neoplasms in the United States (colon, breast, lung) will be obtained from surgical caseloads at the two UCDMC teaching hospitals. Blood, colon, breast, lung, liver, skin, skeletal muscle, lymph nodes, and adipose tissue will be collected when available from informed consenting surgical patients. It is planned to variation of about 10% for tissue levels based on isotopic ratios in blood (Furr et al., (1989a) Am. J. Clin. Nutr. 49:713-716, appended). Deuterium labelled vitamin A (Clifford et al., (1989( Methods in Enzymology, In Press, appended) and beta-carotene will be given orally to subjects 5 or more days before surgery as scheduling permits in amounts equal to that in about 3 multivitamin pills. Vitamin A and beta-carotene will be extracted from blood and tissues and purified and quantified by HPLC. Ratios of labelled to unlabelled vitamins in blood will be determined by GC/MS (vitamin A) and by LC/MS (beta- carotene). The ability to predict tissue nutrient levels from blood measurements is important because current epidemiologic evidence relating diet to human disease risk is limited to correlation among nutrient intake, blood nutrient levels (which are assumed to reflect tissue levels) and the incidence of various diseases. Since nutrients function at and disease begins at the cellular and tissue level, an improved ability to predict tissue levels from blood measurements is desirable.
