Chemoprevention of azoxymethane-induced intestinal carcinogenesis by a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, in rats.

Abstract

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.

• Authors: T Kawamori, T Tanaka, M Suzui, K Okamoto, Y Tamai, M Torihara, J Yamahara, H Mori
• Journal: Carcinogenesis (Carcinogenesis) Vol. 16 Issue 4 Pg. 795-800 (Apr 1995) ISSN: 0143-3334 [Print] England
• PMID: 7728957 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents
• Biomarkers, Tumor
• Retinoids
• KYN 54
• Ornithine Decarboxylase
• Bromodeoxyuridine
• Azoxymethane
• 4-Butyrolactone

Topics

• 4-Butyrolactone (analogs & derivatives, therapeutic use)
• Animals
• Anticarcinogenic Agents (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Azoxymethane
• Biomarkers, Tumor (metabolism)
• Bromodeoxyuridine (metabolism)
• Colon (drug effects, enzymology, metabolism)
• Dose-Response Relationship, Drug
• Epithelium (enzymology, metabolism)
• Intestinal Neoplasms (chemically induced, prevention & control)
• Male
• Ornithine Decarboxylase (metabolism)
• Precancerous Conditions (prevention & control)
• Rats
• Rats, Inbred F344
• Retinoids (therapeutic use)