Inhibition of azoxymethane-induced colon carcinogenesis in male F344 rats by the citrus limonoids obacunone and limonin

Citation
T. Tanaka et al., Inhibition of azoxymethane-induced colon carcinogenesis in male F344 rats by the citrus limonoids obacunone and limonin, CARCINOGENE, 22(1), 2001, pp. 193-198
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
22
Issue
1
Year of publication
2001
Pages
193 - 198
Database
ISI
SICI code
0143-3334(200101)22:1<193:IOACCI>2.0.ZU;2-X
Abstract
The modifying effects of dietary administration of the citrus limonoids oba cunone and limonin on azoxymethane (AOM)-induced colon tumorigenesis were i nvestigated in two experiments in male F344 rats. In a pilot study, we exam ined the modifying effects of obacunone and limonin on AOM-induced (20 mg/k g body wt, once a week for 2 weeks) formation of aberrant crypt foci (ACF), Dietary feeding of both compounds at dose levels of 200 and 500 p.p.m. dur ing AOM exposure for 4 weeks ('initiation' feeding) or after AOM treatment for 4 weeks ('post-initiation' feeding) significantly inhibited ACF formati on (55-65% reduction by 'initiation' feeding, P < 0.001; 28-42% reduction b y 'post-initiation' feeding, P < 0.05-0.002). In a long-term study designed to confirm the protective effects of obacunone and limonin on ACF developm ent, one group was treated with AOM alone and another four groups received the carcinogen treatment plus diets containing 500 p.p.m. test compounds fo r 3 weeks (initiation phase) or 29 weeks (post-initiation phase). Two group s were treated with obacunone or limonin alone (500 p.p.m. in diet) and one group was maintained on the basal diet. At the termination of the study, d ietary exposure to obacunone or limonin during the initiation phase was fou nd to have significantly reduced the incidence of colonic adenocarcinoma (7 2 versus 25 or 6%, P = 0.004 or 0.00003). Obacunone or limonin feeding duri ng the postinitiation phase also reduced the frequency of colonic adenocarc inoma (72 versus 13%, P = 0.0002). Our results suggest that the citrus limo noids obacunone and limonin might be useful for the prevention of human col on cancers.