Suppression of intestinal crypt cell proliferation and aberrant crypt foci by dietary quercetin in rats.
Quercetin inhibits proliferation of human gastric and colonic cancer cells in vitro by suppressing mitosis and increasing apoptosis. Quercetin might therefore act as an anticarcinogen in the alimentary tract, but previous findings have been inconsistent. We fed rats quercetin at dietary concentrations of 1, 5, 20, and 50 g/kg. At < or = 20 g/kg, we observed a statistically significant reduction in the frequency of crypt cell mitosis in proximal, mid, and distal small intestine and in distal colon, amounting to approximately 40% of control at 1 g/kg. There was no effect on apoptosis. Quercetin metabolites, but not quercetin aglycone, were detected in plasma of rats fed quercetin at 20 and 50 g/kg. In a second experiment, rats were fed quercetin at 1 g/kg after treatment with 1,2-dimethylhydrazine to induce aberrant crypt foci. In dimethylhydrazine-treated and control rats, crypt cell mitosis was suppressed at 48 h and 42 days after injection, and there was a statistically significant reduction in the number of aberrant crypts and larger aberrant crypt foci (> 4 crypts/focus) in the distal colon of treated animals. These findings demonstrate that quercetin can inhibit intestinal crypt cell proliferation in vivo, but the effect diminishes as the level of dietary exposure increases. At low concentrations, dietary quercetin inhibits induction of aberrant crypts by a mechanism that does not involve increased crypt cell apoptosis.
Gee
Jennifer M
JM
Institute of Food Research Norwich Laboratory, Norwich Research Park, Colney, Norwich, Norfolk NR4 7UA, UK. jenny.gee@bbsrc.ac.uk
Hara
Hiroshi
H
Johnson
Ian T
IT
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008938:Mitosis / Q000187:drug effects; D011794:Quercetin / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D011794:Quercetin; D019813:1,2-Dimethylhydrazine