Modifying effects of a flavonoid morin on azoxymethane-induced large bowel tumorigenesis in rats.
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.
Tanaka
T
T
First Department of Pathology and Department of Otolaryngology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan. takutt@kanaza-med.ac.jp
Kawabata
K
K
Kakumoto
M
M
Makita
H
H
Ushida
J
J
Honjo
S
S
Hara
A
A
Tsuda
H
H
Mori
H
H
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000236:Adenoma / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001397:Azoxymethane; D002273:Carcinogens; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000627:therapeutic use*; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D011073:Polyamines / Q000378:metabolism; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D047309:Flavones
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D001397:Azoxymethane; D002273:Carcinogens; D005419:Flavonoids; D005982:Glutathione Transferase; D011073:Polyamines; C008548:morin; D047309:Flavones