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.
The entrapment of heterocyclic aromatic amine gastrointestinal (GI) carcinogens (HAAs), by retrievable semipermeable 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[]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 putatative 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 analysis of the urinary metabolites showed there to be lower sulfotransferase activity than in the LF/LB/HNSP group. The amount of 14C-labelled PhIP entrapped by PEI microcapsules was 1.5% of the dose in rodents fed a LF/HB/LNSP human diet and binding was 7-fold higher than in rodents fed a semi-purified diet. These results demonstrate that microcapsules can entrap IQ and PhIP and their metabolites within the GI tract of rodents. The amounts entrapped by microcapsules in the rodent model suggests that this approach may be feasible for human biomonitoring of HAAs and for non-invasively studying dietary modulations of carcinogen exposure within a potential HAA target organ at high risk from as-yet unidentified causes.
O'Neill
I
I
International Agency for Research on Cancer, Lyon, France.
Ohgaki
H
H
Ellul
A
A
Turesky
R J
RJ
D000327:Adsorption; D000818:Animals; D002273:Carcinogens / Q000302:isolation & purification* / Q000378:metabolism / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000139:chemically induced; D004032:Diet; D004064:Digestive System / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000302:isolation & purification* / Q000378:metabolism / Q000633:toxicity; D008280:Magnetics; D008297:Male; D008863:Microspheres; D009153:Mutagens / Q000378:metabolism; D011094:Polyethyleneimine; D011804:Quinolines / Q000302:isolation & purification* / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012306:Risk
D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D011094:Polyethyleneimine; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine