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Food Chem Toxicol. 2008 Mar;46(3):1014-24. Epub 2007 Nov 4.

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

Simonich MTMcQuistan TJubert CPereira CHendricks JDSchimerlik MZhu BDashwood RHWilliams DEBailey GS.

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.

 

 

We recently reported that chlorophyll (Chl) strongly inhibits aflatoxin B(1) preneoplasia biomarkers in rats when administered by co-gavage (Simonich et al., 2007.

Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat. Carcinogenesis 28, 1294-1302.).

The present study extends this by examining the effects of dietary Chl 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 Chl, for 4 weeks. DBP induced high tumor incidences in liver (51%) and stomach (56%), whereas Chl 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.

Chl complexed with DBP in vitro (2Chl:DBP, K(d1)=4.44+/-0.46 microM, K(d2)=3.30+/-0.18 microM), as did CHL (K(d1)=1.38+/-0.32 microM, K(d2)=1.17+/-0.05 microM), possibly explaining their ability to inhibit DBP uptake into the liver by 61-63% (P<0.001).

 

This is the first demonstration that dietary Chlorophyll can reduce tumorigenesis in any whole animal model, and that it may do so by a simple, species-independent mechanism.

 

 

 

 

Carcinogenesis. 2007 Jun;28(6):1294-302. Epub 2007 Feb 8.

Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat.

Simonich MTEgner PARoebuck BDOrner GAJubert CPereira CGroopman JDKensler TWDashwood RHWilliams DEBailey GS.

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.

Chemoprevention by chlorophyll (Chl) was investigated in a rat multi-organ carcinogenesis model.

Twenty-one male F344 rats in three gavage groups (N = 7 rats each) received five daily doses of 250 microg/kg [(3)H]-aflatoxin B(1) ([(3)H]-AFB(1)) alone, or with 250 mg/kg chlorophyllin (CHL), or an equimolar amount (300 mg/kg) of Chl. CHL and Chl reduced hepatic DNA adduction by 42% (P = 0.031) and 55% (P = 0.008), respectively, AFB(1)-albumin adducts by 65% (P < 0.001) and 71% (P < 0.001), respectively, and the major AFB-N(7)-guanine urinary adduct by 90% (P = 0.0047) and 92% (P = 0.0029), respectively.

To explore mechanisms, fluorescence quenching experiments established formation of a non-covalent complex in vitro between AFB(1) and Chl (K(d) = 1.22 +/- 0.05 microM, stoichiometry = 1Chl:1AFB(1)) as well as CHL (K(d) = 3.05 +/- 0.04 microM; stoichiometry = 1CHL:1AFB(1)). The feces of CHL and Chl co-gavaged rats contained 137% (P = 0.0003) and 412% (P = 0.0048) more AFB(1) equivalents, respectively, than control feces, indicating CHL and Chl inhibited AFB(1) uptake.

However, CHL or Chl treatment in vivo did not induce hepatic quinone reductase (NAD(P)H:quinone oxidoreductase) or glutathione S-transferase (GST) above control levels.

These results are consistent with a mechanism involving complex-mediated reduction of carcinogen uptake, and do not support a role for phase II enzyme induction in vivo under these conditions.

In a second study, 30 rats in three experimental groups were dosed as in study 1, but for 10 days.

At 18 weeks, CHL and Chl had reduced the volume percent of liver occupied by GST placental form-positive foci by 74% (P < 0.001) and 77% (P < 0.001), respectively compared with control livers.

CHL and Chl reduced the mean number of aberrant crypt foci per colon by 63% (P = 0.0026) and 75% (P = 0.0004), respectively.

These results show Chlorophyll and Chlorophyllin provide potent chemoprotection against early biochemical and late pathophysiological biomarkers of AFB(1) carcinogenesis in the rat liver and colon.

 

PMID: 17290047 [PubMed - indexed for MEDLINE]

 



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