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

Carcinogenesis. 1995 Apr;16(4):795-800. doi: 10.1093/carcin/16.4.795.

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.

Publication types

  • Comparative Study

MeSH terms

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

Substances

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