Entrapment by magnetic microcapsules of the protein pyrolysates IQ, PhIP and Glu-P-1, and alteration of IQ metabolite exposure within the rat gastrointestinal tract by risk-modulating components of the human diet

I. O'neill, H. Ohgaki, A. Ellul, R. J. Turesky

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6 Scopus citations

Abstract

The entrapment of heterocyclic aromatic amine gastrointestinal (GI) carcinogens (HAAs), by retrievable semi-permeable magnetic polyethylenimine (PEI) microcapsules was investigated in vitro and in vivo as an approach for human biomonitoring. Previous studies showed that PEI microcapsules successfully entrapped benzo[a]pyrene (B[a]P) and its metabolites in the GI tract of rodents. In this study, we have shown that 14C-labelled 2-amino-3-methylimidazo[4,5f] quinoline (IQ), 2-amino-1-methylphenylimidazo[4,5-b] pyridine (PhIP) and 2-amino-6-methyldipyrido]1,2-a:3'2'-d] imidazole (Glu-P-1) are adsorbed to PEI microcapsules in vitro and can be desorbed by treatment with ammoniac methanol. Binding of HAAs to PEI microcapsules containing copper phthalocyanine (TCPTS), a moiety which reversibly binds chemicals with aromatic planar structures, was 2- to 4-fold higher than with unmodified PEI microcapsules. PEI microcapsules also acted as a nucleophile and trapped the proximate carcinogenic metabolite of IQ, 2-hydroxy-amino-3-methyl-imidazo[4,5f]quinoline (N-hydroxy-IQ). The entrapment of 14C-labelled IQ and PhIP by microcapsules was investigated in vivo in male F344 rats fed a conventional chow diet or a human diet with varying amounts of fat and beef intake typically consumed in the UK. Animals were adapted to human diets which were either high (H) or low (L) in fat (F), beef protein (B) and dietary fibre non-starch polysaccharide (NSP). Microcapsule entrapment of IQ and metabolites was 0.5-2.0% of the dose and 4-fold higher in rats consuming a HF/HB/LNSP than those consuming a LF/LB/HNSP diet, these being respectively putative high- and low-risk-associated diets. In the HF/HB/LNSP diet group, a higher amount of IQ metabolites were detected in the microcapsules; a lower proportion of covalently bound metabolites could be removed by acid hydrolysis. Urinary excretion was 2-fold greater and

Original languageEnglish (US)
Pages (from-to)2353-2359
Number of pages7
JournalCarcinogenesis
Volume13
Issue number12
DOIs
StatePublished - Dec 1992

Bibliographical note

Funding Information:
We gratefully acknowledge the supply of human diets by Dr Sheila Bingham, Dunn Nutrition Centre, Cambridge, arid a gift of radiolabeUed protein pyrolysates by Dr T.Sugimura, National Cancer Institute, Tokyo. NIH-07 diet was kindly provided by DrJ.Huff (NIEHS). We thank Dr A.Shah for experimental assistance and Mme P.Collard for the preparation of this manuscript. We thank US National Institutes of Health for partial support of this work (CA 39417).

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