| The carotenoid lycopene (lyc) has emerged as a primary chemopreventative agent for prostate cancer. The first objective was to determine if pre-feeding lyc decreased absorption, altered tissue distribution or increased metabolism of a single oral dose of 14C-lyc compared to control pre-fed rats. F344 rats (n=48) were pre-fed either a control (CP) or lyc-enriched (LP) diet (0.25g lyc/kg diet) for 30d and euthanized at 5 or 24h after a 14C-lyc dose. The percent 14C absorption at 24h was lower in LP rats than in CP rats (P<0.04). Hepatic total 14C and 14C-lyc in CP rats was greater than in LP rats at 24h (P<0.005). Extra-hepatic tissues took up 14C as early as 5h, irrespective of diet. Percent 14C-polar products increased over time in the prostate and seminal vesicles, but not in other tissues analyzed, irrespective of previously fed diet.; The second objective was to clone the carotenoid cleavage enzyme, carotenoid 9',10'-monoxygenase II (CMOII) in the rat model, to determine if feeding lyc for different periods of time (3-37d) resulted in altered expression of genes related to carotenoid cleavage [carotenoid 15,15' monoxygenase I (CMOI), CMOII and peroxisomal proliferators activated receptor gamma (PPARgamma)] and to measures elected phase I and phase II detoxification enzyme activities in tissues. The rat CMOII gene was successfully cloned. The gene expression results could be divided into three groups: tissues where the gene(s) expression increased (SI mucosa and liver); decreased (prostate, kidney, and adrenal); or were maintained (testes and lung) with lyc feeding. Lyc did not alter hepatic phase I activity or lung and kidney quinone reductase activity but it increased hepatic quinone reductase activity after 3 and 7d of lyc feeding.; This research has shown that lyc metabolites accumulate in the prostate, seminal vesicles and adrenal gland compared to the other analyzed tissues. Moreover, modulated carotenoid cleavage enzyme(s) expression in the adrenal, prostate and kidney suggested that the accumulated lyc metabolites in these tissues be involved in the observed transcriptional changes. In essence, lyc has previously been reported to improve antioxidant status but the presented data suggests that lyc could also modulate prostate cancer related genes. |
