Carcinogenesis, Vol 18, 957-965, Copyright © 1997 by Oxford University Press
T Tanaka, H Makita, K Kawabata, H Mori, M Kakumoto, K Satoh, A Hara, T Sumida, T Tanaka and H Ogawa
The modulating effects of dietary feeding of two flavonoids, diosmin and
hesperidin, both alone and in combination, during the initiation and
post-initiation phases on colon carcinogenesis initiated with azoxymethane
(AOM), were investigated in male F344 rats. Animals were initiated with AOM
by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon
neoplasms. Rats were fed the diets containing diosmin (1000 ppm),
hesperidin (1000 ppm) or diosmin (900 ppm) + hesperidin (100 ppm) for 5
weeks (initiation treatment) or 28 weeks (post-initiation treatment). The
others contained the groups of rats treated with diosmin, hesperidin alone
or in combination, and untreated. At the end of the study (32 weeks), the
incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the
large intestine of rats initiated with AOM together with, or followed by, a
diet containing diosmin or hesperidin were significantly smaller than those
of rats given AOM alone (P <0.001). The combination regimen during the
initiation and post-initiation stages also inhibited the development of
colonic neoplasms, but the tumor data did not indicate any beneficial
effect of diosmin and hesperidin administered together as compared with
when these agents were given individually. In addition, feeding of diosmin
and hesperidin, both alone and in combination, significantly inhibited the
development of aberrant crypt foci. As for cell proliferation biomarkers,
dietary exposure of diosmin and hesperidin significantly decreased the
5'-bromodeoxyuridine- labeling index and argyrophilic nuclear organizer
region's number in crypt cells, colonic mucosal ornithine decarboxylase
activity, and polyamine levels in the blood. These results indicate that
diosmin and hesperidin, both alone and in combination, act as a
chemopreventive agent against colon carcinogenesis, and such effects may be
partly due to suppression of cell proliferation in the colonic crypts,
although precise mechanisms should be clarified.
ARTICLES
Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin
The First Department of Pathology, Gifu University School of Medicine, Gifu City, Japan.
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