CHEMOPREVENTIVE EFFECTS OF CAROTENOIDS AND CURCUMINS ON MOUSE COLON CARCINOGENESIS AFTER 1,2-DIMETHYLHYDRAZINE INITIATION

The present study was carried out to examine the chemopreventive effec ts of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed i n terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation, Five-meek-old B6C3F(1) male mice were divided into three groups, groups 1 and 2 bei ng given DMH (20 mg/kg body wt, s.c.) twice a meek for 3 weeks, Animal s of group 1 were then treated with one of the test compounds, lycopen e (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water an d lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet f rom weeks 5-12, Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone, All animals were killed at me ek 12, Numbers of ACF/mouse in the group I treated with fucoxanthin(47 .1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01), Numbers of aberrant crypts (ACs)/mouse were als o significantly lower after treatment with lutein (79.9 +/- 34.7) or 0 .5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01), BrdU labeling indices (LI) in mice treated with lutein and 0. 5% THC were significantly decreased in both upper and lower half compa rtments of colonic crypts as compared to the controls (P < 0.05 and 0. 01, respectively), especially the upper half data corresponding to red uction of ACs/mouse, The results thus suggest that fucoxanthin, lutein , and THC may have potential as chemopreventive agents against colon c arcinogenesis.