Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of spontaneous liver cancer

The Long-Evans Cinnamon (LEC) rat is a well-characterized model of spontane ous hepatocarcinogenesis. It has been shown that dietary administration of lycopene or the herbal medicine Sho-saiko-to (TJ-9) has anticarcinogenic ac tivity, although the mechanism by which these products protect against carc inogenesis is not well known. We investigated the outcome of administration of lycopene and TJ-9 on the occurrence of hepatic neoplasia in LEC rats. A diet containing 0.005% lycopene (originally the product of tomato oleoresi n containing 13% lycopene) and 1% TJ-9 (crude extracts of 7 herbs: bupleuru m root, pinellia tuber, scutellaria root, jujube fruit, ginseng root, glycy rrhiza root, and ginger rhizome) was administered from 6 weeks of age until the rats were sacrificed at 76 weeks of age, at which time most of the non treated animals were known to have hepatocellular carcinoma (HCC). Developm ent of HCC in treated groups was analyzed histologically by comparison with untreated controls. Glutathione S-transferase placental form (GST-P) was a nalyzed by an immunohistochemical method. Concentration of copper, iron, an d zinc, which appear to play a role in hepatocarcinogenesis in LEC rats, wa s analyzed The percent areas of HCC in the liver specimens of control, lyco pene, and TJ-9 groups were 17.9 +/- 17.1%, 27.2 +/- 20.8%, and 27.6 +/- 18. 4%, respectively. These intergroup differences were not significant. The pe rcent area, number of areas, and mean size of area staining positively for GST-P revealed no significant differences between the groups. The number of GST-P-positive areas within the HCC lesions was greater in the TJ-9 group than in the control or lycopene group (p = 0.024 and p = 0.012, respectivel y). The study also demonstrated a lower concentration of iron in livers of the lycopene group than the control group (p = 0.019). There were no differ ences in serum a-fetoprotein levels or the cumulative survival rates betwee n the groups. In conclusion, long-term administration of lycopene or TJ-9 d id not reduce the risk of hepatocarcinogenesis in LEC rats.