Carcinogenesis, Vol 19, 919-924, Copyright © 1998 by Oxford University Press
RJ Mauthe, EG Snyderwine, A Ghoshal, SP Freeman and KW Turteltaub
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary
carcinogen in female rats and is present in a wide variety of cooked meats.
We address here the excretion of PhIP and its metabolites into the
breast-milk of lactating rats and the ability of chlorophyllin, a food
product derivative with chemopreventive properties, to affect these levels
at low PhIP doses. Lactating female F344 rats with suckling pups were
orally administered 50, 500 and 1000 ng [14C]PhIP/kg body weight. The
excretion of the [14C]PhIP into milk and its distribution among the mammary
tissue, liver and blood of the dam, as well as among stomach contents and
liver of their suckling pups was measured using accelerator mass
spectrometry (AMS). PhIP, PhIP-4'- sulfate, 4'-hydroxy-PhIP, and
N2-hydroxy-PhIP-N3-glucuronide were found in the milk at all doses. The
chlorophyllin (500 microg/kg) co- administration with PhIP (500 ng/kg)
caused increased levels of [14C]PhIP in the milk (32%) and stomach contents
(35%) of the pups relative to the animals not receiving chlorophyllin at
these low PhIP doses. In contrast, lower [14C]PhIP levels in the
chlorophyllin treated animals were observed in the blood (47%) and mammary
tissue (68%) of the dam, as well as the pup's liver tissue (37%) compared
to the animals receiving only PhIP. Chlorophyllin co-administration
resulted in an increased amount of N2-hydroxy-PhIP-N3-glucuronide (42%),
increased PhIP (79%) and decreased levels of PhIP-4'-sulphate (77%)
relative to the animals not receiving chlorophyllin. These results suggest
that PhIP and PhIP metabolites are present in the breast-milk of lactating
rats at human dietary PhIP exposures and that PhIP is absorbed by the
newborn. Furthermore, these results suggest that other dietary components
can affect the dosimetry of PhIP in breast-feeding offspring.
ARTICLES
Distribution and metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) in female rats and their pups at dietary doses
Molecular and Structural Biology Division and Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA 94551, USA.
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