Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

β-ionone (βI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight), GO (25 mg/100 g body weight), βI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the βI (91 ± 11 and 14 ± 3) and βI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry) were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcrvpdate=20110329inogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

Effects of crude extracts of Agaricus blazei on DNA damage and on rat liver carcinogenesis induced by diethylnitrosamine

The effects of crude extracts of the mushroom Agaricus blazei Murrill (Agaricaceae) on both DNA damage and placental form glutathione S-transferase (GST-P)-positive liver foci induced by diethylnitrosamine (DEN) were investigated. Six groups of adult male Wistar rats were used. For two weeks, animals of groups 3 to 6 were treated with three aqueous solutions of A. blazei (mean dry weight of solids being 1.2, 5.6, 11.5 and 11.5 mg/ml, respectively). After this period, groups 2 to 5 were given a single ip injection 200 mg/kg DEN and groups 1 and 6 were treated with 0.9 NaCl. All animals were subjected to 70 partial hepatectomy at week five and sacrificed 4, 24 and 48 h or 8 weeks after DEN or 0.9 NaCl treatments (10th week after the beginning of the experiment). The alkaline comet assay and GST-P-positive liver foci development were used to evaluate the influence of the mushroom extracts on liver cell DNA damage and on the initiation of liver carcinogenesis, respectively. Previous treatment with the highest concentration of A. blazei (11.5 mg/ml) significantly reduced DNA damage, indicating a protective effect against DEN-induced liver cytotoxicity/genotoxicity. However, the same dose of mushroom extract significantly increased the number of GST-P-positive liver foci