Carcinogenesis Advance Access published online on February 17, 2005
Carcinogenesis, doi:10.1093/carcin/bgi047
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1 Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
* To whom correspondence should be addressed. Chemopreventive activities of the isoprenoids geranylgeraniol (GGO) and
Received November 5, 2004
Revised February 1, 2005
Accepted February 6, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Geranylgeraniol and
-ionone inhibit hepatic preneoplastic lesions, cell proliferation, total plasma cholesterol and DNA damage during the initial phases of hepatocarcinogenesis, but only the former inhibits NF-
B activation
Fernando Salvador Moreno, E-mail: RMORENO{at}USP.BR
Abstract 
-ionone (BI) were evaluated during initial phases of hepatocarcinogenesis. Rats received daily during 7 weeks 8 or 16 mg/100 g body weight GGO (GGO8 and GGO16 groups) or BI (BI8 and BI16 groups), or only corn oil (CO group, controls). Incidence (%) and mean number of visible hepatocyte nodules/animal were inhibited in GGO8 (64% and 21±40), GGO16 (33% and 3±5), BI8 (50% and 13±34) and BI16 (42% and 9±19) groups compared to CO group (100% and 34±51) (P < 0.05, except for GGO8 group). Number/cm2 liver section, mean area (mm2) and % liver section area occupied by persistent hepatic placental glutathione S-transferase positive preneoplastic lesions (PNL) were reduced in GGO8 (11±9; 0.26±0.35; 2.7±3.0), GGO16 (6±6; 0.18±0.16; 0.9±0.9), BI8 (9±5; 0.13±0.20; 1.1±1.2) and BI16 (8±6; 0.08±0.09; 0.6±0.4) groups compared to CO group (26±18; 0.29±0.34; 7.0±5.5) (P < 0.05). GGO16 and BI16 groups showed smaller visible hepatocyte nodules, reduced PNL cell proliferation and total plasma cholesterol levels compared to CO group (P < 0.05), but no differences (P > 0.05) in PNL apoptosis. DNA damage expressed as comet length (mm) was reduced in GGO8 (96.7±1.5), GGO16 (94.2±1.5), BI8 (97.1±1.1) and BI16 (95.1±1.5) groups compared to CO group (102.1±1.7) (P < 0.05). Compared to normal animals, CO group animals showed increased (P < 0.05) nuclear levels of nuclear factor kappa B (NF-
B) p65 subunit in hepatic cells, which were decreased (P < 0.05) in GGO16 group animals. Anticarcinogenic actions of these isoprenoids seem to follow a dose-response relationship. Results indicate that GGO and BI represent promising chemopreventive agents against hepatocarcinogenesis. Inhibition of cell proliferation and DNA damage seems to be important for the isoprenoids’ anticarcinogenic actions, while inhibition of NF-B activation seems to be specifically related to GGO actions.
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