Low-dose dietary chlorophyll inhibits multi-organ carcinogenesis in the rainbow

We recently reported that chlorophyll (Chi) strongly inhibits aflatoxin 131 preneoplasia biomarkers in rats when administered by co-gavage (Simonich et at., 2007. Natural chlorophyll inhibits aflatoxin B I-induced multi-organ carcinogenesis in the rat. Carcinogenesis 28,1294-1302.). The present study extends this by examining the effects of dietary Chi on tumor development, using rainbow trout to explore ubiquity of mechanism. Duplicate groups of 140 trout were fed diet containing 224 ppm dibenzo[a,l]pyrene (DBP) alone, or with 1000-6000 ppm Chi, for 4 weeks. DBP induced high tumor incidences in liver (51%) and stomach (56%), whereas Chi co-fed at 2000, 4000 or 6000 ppm reduced incidences in stomach (to 29%, 23% and 19%, resp., P < 0.005) and liver (to 21%, 28% and 26%, resp., P < 0.0005). Chlorophyllin (CHL) at 2000 ppm gave similar protection. Chi complexed with DBP in vitro (2Chl:DBP, K-d1 = 4.44 +/- 0.46 mu M, K-d2 = 3.30 +/- 0.18 mu M), as did CHL (K-d1= 1.38 +/- 0.32 mu M, K-d2 = 1.17 +/- 0.05 mu M), possibly explaining their ability to inhibit DBP uptake into the liver by 61-63% (P < 0.001). This is the first demonstration that dietary Chi can reduce tumorigenesis in any whole animal model, and that it may do so by a simple, species-independent mechanism. (c) 2007 Elsevier Ltd. All rights reserved.