Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats.
The modifying effects of dietary administration of ferulic acid (FA) on azoxymethane (AOM)-induced colon carcinogenesis were examined in three experiments with male 344 rats. In the first experiment, the modifying effect of FA on AOM (15 mg/kg body weight, once a week, for 3 weeks)-induced formation of aberrant crypt foci (ACF) was examined in five groups. Numbers of ACF/colon of groups 2 (AOM+250 ppm FA) and 3 (AOM+500 ppm FA) at the termination (5 weeks after the start) were smaller than of group 1 (AOM alone). Those of ACF/cm(2) of group 3 were also smaller than of group 1 (P<0.05). In the second experiment, a long-term assay for the effects of FA was conducted with seven groups. At the termination (35 weeks), groups 2 and 3 which were given FA during the initiation phase at doses of 250 and 500 ppm, respectively, had lower incidences of colonic carcinomas (23 and 27%, respectively) than group 1 which was given AOM alone (59%; P<0.05). In the third experiment, to determine whether FA could modify the activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR) in liver and colon, 60 rats were gavaged with FA at four doses (0, 25, 50, 100 mg/kg body weight). Dosing of 100 mg/kg significantly elevated GST activity in liver (P<0.03), and QR activities in liver and colonic mucosa (P<0.01 and P<0.02, respectively), suggesting that detoxifying enzymes are related to the blocking effect of FA on AOM-induced colon carcinogenesis.
Kawabata
K
K
Department of Pathology, Gifu University School of Medicine, Tsukasa-machi, Japan.
Yamamoto
T
T
Hara
A
A
Shimizu
M
M
Yamada
Y
Y
Matsunaga
K
K
Tanaka
T
T
Mori
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use* / Q000633:toxicity; D001397:Azoxymethane / Q000037:antagonists & inhibitors; D002273:Carcinogens; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D003373:Coumaric Acids / Q000627:therapeutic use* / Q000633:toxicity; D004032:Diet; D005982:Glutathione Transferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D003373:Coumaric Acids; C004999:ferulic acid; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D001397:Azoxymethane