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.