X-Message-Number: 27798
Date: Tue, 4 Apr 2006 06:12:14 -0700 (PDT)
From: Doug Skrecky <>
Subject: rodent chow can block the benefit of anticarcinogens

[Curious effect!]

J Nutr. 2004 Dec;134(12 Suppl):3445S-3452S.
Chemoprevention by grape seed extract and genistein in
carcinogen-induced mammary cancer in rats is diet dependent.
  Many popular dietary supplements are enriched in polyphenols
such as the soy isoflavones, tea catechins, and resveratrol
(from grape skins), each of which has been shown to have
chemopreventive activity in cellular models of cancer. The
proanthocyanidins, which are oligomers of the catechins, are
enriched in grape seeds and form the basis of the dietary supplement
grape seed extract (GSE). Evidence suggests that the
proanthocyanidins may be metabolized to the monomeric catechins.
This study was carried out to determine whether GSE added to rodent
diets protected against carcinogen-induced mammary tumorigenesis in
rats and whether this was affected by the composition of the whole
diet. Female rats were begun on 5%, 1.25%, or 0% (control)
GSE-supplemented diets at age 35 d. At age 50 d they were
administered 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil
at 80 mg/kg body weight. They were weighed and monitored weekly for
tumor development until 120 d after DMBA administration.
Administration of GSE in AIN-76A diet did not show any protective
activity of GSE against DMBA-induced breast cancer. However,
administration of GSE in a laboratory dry food diet (Teklad 4% rodent
diet) resulted in a 50% reduction in tumor multiplicity. In similar
experiments, genistein administered in AIN-76A diet also failed to
show chemopreventive activity against the carcinogen
N-methyl-N-nitrosourea; however, when administered at the same dose
in the Teklad 4% rodent diet, genistein exhibited significant
chemopreventive activity (44-61%). These results demonstrate that
GSE is chemopreventive in an animal model of breast cancer; moreover,
the diet dependency of the chemopreventive activity for both GSE and
genistein suggests that whether or not a compound is chemopreventive
may depend on the diet in which the agent is administered.

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