Quercetin, but not its glycosidated conjugate rutin, inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats
de Boer, V.C.J.
van der Woude, H.
TNO Kwaliteit van Leven
The effect of the flavonoid quercetin and its conjugate rutin was investigated on (biomarkers of) colorectal cancer (CRC). Male F344 rats (n = 42/group) were fed 0, 0.1, 1, or 10 g quercetin/kg diet or 40 g rutin/kg diet. Two wk after initial administration of experimental diets, rats were given 2 weekly subcutaneous injections with 15 mg/kg body wt azoxymethane (AOM). At wk 38 post-AOM, quercetin dose dependently (P < 0.05) decreased the tumor incidence, multiplicity, and size, whereas tumor incidences were comparable in control (50%) and rutin (45%) groups. The number of aberrant crypt foci (ACF) in unsectioned colons at wk 8 did not correlate with the tumor incidence at wk 38. Moreover, at wk 8 post-AOM, the number and multiplicity of ACF with or without accumulation of β-catenin were not affected by the 10 g quercetin/kg diet. In contrast, another class of CRC-biomarkers, β-catenin accumulated crypts, contained less β-catenin than in controls (P < 0.05). After enzymatic deconjugation, the plasma concentration of 3′-O-methyl-quercetin and quercetin at wk 8 was inversely correlated with the tumor incidence at wk 38 (r = -0.95, P ≤ 0.05). Rats supplemented with 40 g rutin/kg diet had only 30%of the (3′-O-methyl-) quercetin concentration of 10 g quercetin/kg diet-fed rats (P < 0.001). In conclusion, quercetin, but not rutin, at a high dose reduced colorectal carcinogenesis in AOM-treated rats, which was not reflected by changes in ACF-parameters. The lack of protection by rutin is probably due to its low bioavailability. © 2006 American Society for Nutrition.
To reference this document use:
Toxicology and Applied Pharmacology
Rats, Inbred F344
Journal of Nutrition, 136 (11), 2862-2867