Carcinogenesis, Vol. 20, No. 8, 1477-1484,
August 1999
© 1999 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Modifying effects of a flavonoid morin on azoxymethane-induced large bowel tumorigenesis in rats
First Department of Pathology and
1 Department of Otolaryngology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293,
2 Department of Pathology and
3 Department of Oral Surgery, Gifu University School of Medicine, 40 Tukasa-machi, Gifu 500-8076,
4 Department of Biochemistry, Gifu Pharmaceutical University 5-6-1 Mitahorahigashi, Gifu 502-0003 and
5 Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
The modifying effect of dietary exposure to a flavonoid morin during the initiation and post-initiation phases of azoxymethane (AOM)-initiated colorectal carcinogenesis was investigated in male F344 rats. A total of 55 animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induce colorectal neoplasms. Rats were fed a diet containing 500 p.p.m. morin for 5 (`initiation feeding') or 28 (`post-initiation feeding') weeks. Other groups contained rats treated with morin alone (500 p.p.m. in diet) and untreated rats. At the end of the study (32 weeks), the incidence of adenocarcinoma in the large intestine of rats initiated with AOM together with (43%) or followed by (29%) a diet containing morin was smaller than that of rats given AOM alone (75%). A significant difference was found between `post-initiation feeding' and untreated groups (P = 0.023). Although both `initiation feeding' and `post-initiation feeding' of morin reduced polyamine levels in colorectal mucosa and blood, `post-initiation feeding' of morin significantly decreased the proliferating cell nuclear antigen-positive index in aberrant crypt foci. `Post-initiation feeding' of morin significantly elevated glutathione S-transferase and quinone reductase activities in the liver and large bowel, but `initiation feeding' caused a significant elevation of these enzymes activities only in the large bowel. These results indicate that morin could exert a weak chemopreventive effect on large bowel tumorigenesis induced by AOM when fed during the post-initiation phase.
Abbreviations: ACF, aberrant crypt foci; AOM, azoxymethane; COX, cyclooxygenase; GST, glutathione S-transferase; LOX, lipoxygenase; PCNA, proliferating cell nuclear antigen; QR, quinone reductase officially designated NAD(P)H:(quinone acceptor) oxidoreductase and also known as DT-diaphorase or menadione reductase
6 To whom correspondence should be addressed Email: takutt{at}kanazawa-med.ac.jp
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