DISTRIBUTION AND METABOLISM OF 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) IN FEMALE RATS AND THEIR PUPS AT DIETARY DOSES

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary ca rcinogen in female rats and is present in a wide variety of cooked mea ts. We address here the excretion of PhIP and its metabolites into the breast-milk of lactating rats and the ability of chlorophyllin, a foo d product derivative with chemopreventive properties, to affect these levels at low PhIP doses. Lactating female F344 rats with suckling pup s were orally administered 50, 500 and 1000 ng [C-14]PhIP/kg body weig ht. The excretion of the [C-14]PhIP into milk and its distribution amo ng the mammary tissue, liver and blood of the dam, as well as among st omach contents and liver of their suckling pups was measured using acc elerator mass spectrometry (AMS), PhIP, PhIP-4'-sulfate, 4'-hydroxy-Ph IP, and N-2-hydroxy-PhIP-N-3-glucuronide were found in the milk at all doses. The chlorophyllin (500 mu g/kg) co-administration with PhIP (5 00 ng/kg) caused increased levels of [C-14]PhIP in the milk (32%) and stomach contents (35%) of the pups relative to the animals not receivi ng chlorophyllin at these low PhIP doses. In contrast, lower [C-14]PhI P levels in the chlorophyllin treated animals were observed in the blo od (47%) and mammary tissue (68%) of the dam, as well as the pup's liv er tissue (37%) compared to the animals receiving only PhIP, Chlorophy llin co-administration resulted in an increased amount of N-2-hydroxy- PhIP-N-3-glucuronide (42%), increased PhIP (79%) and decreased levels of PhIP-4'-sulphate (77%) relative to the animals not receiving chloro phyllin. These results suggest that PhIP and PhIP metabolites are pres ent in the breast-milk of lactating rats at human dietary PhIP exposur es and that PhIP is absorbed by the newborn. Furthermore, these result s suggest that other dietary components can affect the dosimetry of Ph IP in breast-feeding offspring.