A xanthine oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats.
The modifying effect of dietary administration of a xanthine oxidase inhibitor 1'-acetoxychavicol acetate (ACA) present in an edible plant Languas galanga in Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce colonic ACF. They were fed the diets containing 100 or 200 ppm ACA for 5 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (week 5), AOM induced 118 +/- 28 ACF/colon. Dietary administration of ACA caused significant reduction in the frequency of ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition by 200 ppm ACA feeding, P<0.01). Such inhibition might be associated with suppression of the proliferation biomarkers' expression such as ornithine decarboxylase activity in the colonic mucosa, number of silver-stained nucleolar organizer regions' protein in the colonic mucosal cell nuclei and blood polyamine content. These results indicate that ACA could inhibit the development of AOM-induced ACF through its suppression of cell proliferation in the colonic mucosa and ACA might be a possible chemopreventive agent against colon tumourigenesis.
Tanaka
T
T
First Department of Pathology, Gifu University School of Medicine, Tsukasa-machi, Japan.
Makita
H
H
Kawamori
T
T
Kawabata
K
K
Mori
H
H
Murakami
A
A
Satoh
K
K
Hara
A
A
Ohigashi
H
H
Koshimizu
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D001592:Benzyl Alcohols; D001835:Body Weight; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003108:Colonic Diseases / Q000139:chemically induced*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000097:blood; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D013729:Terpenes / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D001592:Benzyl Alcohols; D004791:Enzyme Inhibitors; D011073:Polyamines; D013729:Terpenes; D014969:Xanthine Oxidase; D009955:Ornithine Decarboxylase; D001397:Azoxymethane; C047948:1'-acetoxychavicol acetate