Binding of benzo[a]pyrene metabolites in the rat intestinal lumen by magnetic polyethyleneimine microcapsules following an intragastric dose of [14C]benzo[a]pyrene

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Abstract
Semi-permeable magnetic polyethyleneimine (PEI) microcapsules have been developed to trap carcinogens and their metabolites in vivo and their time-dependent binding of a model carcinogen, [ 14 C]benzo[a]pyrene ([ 14 C]BaP), is studied within the intestinal lumen. Overall, ∼ 0.5% of an intragastrk BaP dose was bound by these microcapsules recovered from faeces with specific binding of metabolites (nmol/10 6 recovered microcapsules) being similar in the 0–24-h and 24–48-h periods, but ∼ 10-fold lower in the 48–72-h period. Successive extractions of microcapsules with ammoniacal methanol, 2.5 N HCI, methanol and dimethylsulfoxide released ∼ 60% of bound radiolabel and the unextracted radiolabel was presumed to have been bound covalently. By contrast, > 90% of bound radiolabel was extractable from the faeces of the treated animals and from microcapsules treated in vitro with [ 14 C]7,8-dihydroxy-9,10-epoxytetrahydrobenzo[a]-pyrene (BaPDE), indicating that the in vivo microcapsule- bound metabolites were not derived either from adsorbed faecal material or from [ 14 C]BaPDE formed in situ . A time-dependent appearance of BaP 3,6-dione was found. Also the qualitative and quantitative patterns of metabolites trapped by microcapsules, as assayed by h.p.l.c, were consistent only with a unique set of BaP metabolites being bound within the intestinal lumen. Hence these carcinogen-binding microcapsules can be used to investigate the in situ formation of carcinogen metabolites within the intestinal tract.