Chemoprevention of azoxymethane-induced intestinal carcinogenesis by a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, in rats.
The present study was designed to investigate the modifying effects of dietary 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54), a new synthetic retinoidal butenolide, during the post-initiation phase on azoxymethane (AOM)-induced rat intestinal carcinogenesis. The number of aberrant crypt foci (ACF) in rat colon, colonic ornithine decarboxylase (ODC) activity and bromodeoxy-uridine (BrdUrd) labeling index in rat colonic epithelium were also assessed. At 7 weeks of age, male F344 rats (except the KYN-54 alone and control groups) were given weekly s.c. injections of AOM at 15 mg/kg body wt for 3 weeks. Starting 1 week after the last injection of AOM, rats (except the control group) were fed a diet containing KYN-54 at concentrations of 100 or 200 p.p.m. throughout the experiment. All animals were necropsied at 32 weeks after the start of the experiment. Compared with the AOM alone group, KYN-54 at both doses reduced the incidence and multiplicity of tumors in entire intestine (small and large intestines). In the 200 p.p.m. KYN-54 fed group especially, tumor incidence and multiplicity in the entire intestine were lower compared with the AOM alone group (P < 0.005 and P < 0.05 respectively). Also, the number of ACF/cm2 colon in the groups of rats treated with AOM and KYN-54 at both doses were significantly lower than that of rats treated with AOM alone (P < 0.05). Colonic ODC activity and BrdUrd labeling index in the groups of rats treated with AOM and KYN-54 at both doses were slightly lower than those treated with AOM alone. KYN-54 at 200 p.p.m. significantly lowered BrdUrd labeling index induced by AOM (P < 0.005). These results suggest that KYN-54 might be a promising chemopreventive agent for intestinal neoplasia.
Kawamori
T
T
First Department of Pathology, Gifu University School of Medicine, Japan.
Tanaka
T
T
Suzui
M
M
Okamoto
K
K
Tamai
Y
Y
Torihara
M
M
Yamahara
J
J
Mori
H
H
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D014408:Biomarkers, Tumor / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011230:Precancerous Conditions / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D012176:Retinoids / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012176:Retinoids; C077240:KYN 54; D009955:Ornithine Decarboxylase; D001973:Bromodeoxyuridine; D001397:Azoxymethane; D015107:4-Butyrolactone