EXPRESSION OF C-MYC IN HUMAN COLONIC TISSUE IN RESPONSE TO BETA-CAROTENE SUPPLEMENTATION

Dietary supplementation with beta-carotene at 30 mg/day results in an increased serum trans-retinoic acid concentration in patients with a p rior colonic polyp. In a number of human cell lines, trans-retinoic ac id upregulates c-myc mRNA expression. We assayed for changes in c-myc mRNA expression in colonic mucosa by reverse transcription polymerase chain reaction and correlated the results with serum concentrations of all-trans-(ATRA), 13-cis-(13-cRA), and total retinoic acid. Serum and colonic biopsy samples were obtained before and 90 days after adminis tration of a placebo (n = 7) or 30 mg of beta-carotene (n = 5) daily. An increase in c-myc expression after supplementation was observed in 6 of 12 subjects, but 5 of these 6 subjects had decreased total serum retinoic acid concentration and 4 had decreased ATRA concentration. In addition, five of the six subjects with increased c-myc expression ha d received a placebo. Conversely, c-myc expression was increased in on ly two of five paired samples from subjects whose total serum retinoic acid concentration increased during the 90-day supplementation period . We conclude that c-myc expression is nor correlated with ATRA, 13-cR A, or total retinoic acid concentration in vivo and that increased ser um retinoic acid secondary to increased tissue beta-carotene is not su fficient to activate c-myc transcription.