Affiliations: Department of Pathology, Kanazawa Medical University,
Uchinada, Ishikawa 920-0293, Japan | Department of Serology, Kanazawa Medical University,
Uchinada, Ishikawa 920-0293, Japan | Faculty of Pharmaceutical Sciences, Hokkaido Iryo
University, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Note: [] Department of Pathology, Kanazawa Medical University, Uchinada,
Ishikawa 920-0293, Japan. Tel.: +81 76 286 2211 (ext. 3611); Fax: +81 76 286
6926; E-mail: takutt@kanazawa-med.ac.jp
Abstract: Obacunone and limonin are bitter limonoids in citrus. Their
modifying effects on the development of aberrant crypt foci (ACF), the activity
of detoxification enzymes, glutathione S-transferase (GST)
and quinone reductase (QR), and cell proliferation activity were investigated
in male F344 rats treated with azoxymethane (AOM). Obacunone and limonin were
administered in the diet, during the initiation (for 4 weeks) or postinitiation
phase (for 4 weeks) of AOM-induced tumorigenesis. Feeding of obacunone and
limonin (0.02% 0.05%) and 28-42% ability to reduce the proliferating cell
nuclear antigen-labeling index in crypts and correlated well with the
prevention of ACF. In a subsequent long-term experiment (38 weeks), in which
rats were initiated with AOM and fed 0.05% the initiation or post-initiation
phase, both compounds in diet caused significant reduction (65%- colonic
adenocarcinoma. Thus, citrus bitter limonoids obacunone and limonin possess
chemopreventive effects on chemically induced rat colon carcinogenesis.
