title: Novel detection by magnetic microcapsules in the human gastrointestinal tract of cross-linking agents and diet-dependent reactive oxygen species.
abstract: Semi-permeable magnetic microcapsules previously shown able to trap gastrointestinal carcinogens and containing polyethyleneimine (PEI) were covalently labelled with [14CH3], and administered for the first time to humans (six healthy volunteers, 1.3 microCi/dose) in gelatin capsules together with radio-opaque gut transit markers (ROM), in order both to seek human endogenous cross-linking or bifunctional alkylating agents and assess gut transit features. No ill-effects were reported. Faecal ROM and 14C excretions were well correlated (r = 0.96), and net 14C recovery in faeces was 83-96%. Microcapsules were separated magnetically from faeces and 29-81% of specific labelling of microcapsules (nCi/10(6)) was found to have been removed during GI transit. Label cleavage out of these microcapsules was also found following in vitro anaerobic incubation with faecal slurries from two volunteers. On treatment with H2O2, label was removed selectively from the Fe-containing core in a dose-dependent manner. Therefore, label cleavage in vivo (not observed in rats consuming chow but found notably on consumption of low-fibre and/or high-beef human diets) is likely to arise from low mol. wt substances that give Fenton reaction producing hydroxyl radicals and oxidative demethylation. After GI transit, extensive core to membrane cross-linking in the microcapsules was found and was inversely related to faecal output. Cross-linking also was obtained to a greater extent during in vitro anaerobic incubation with faecal slurries. The GI mucosa would also be exposed to both types of agents, and several features of this microcapsule monitoring are in accord with putative risk-modulating effects. This first use of microcapsules for biomonitoring of the human GI tract thus seemed to be without hazard, and revealed extensive levels of agents likely to cause DNA damage.
authors.affiliation: MRC Dunn Clinical Nutrition Centre, Cambridge, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Bingham
authors.forename: A
authors.initials: A
authors.lastname: Ellul
authors.forename: J H
authors.initials: JH
authors.lastname: Cummings
authors.forename: I
authors.initials: I
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D002214:Capsules; D015179:Colorectal Neoplasms / Q000209:etiology; D003432:Cross-Linking Reagents / Q000032:analysis*; D004032:Diet; D004064:Digestive System / Q000378:metabolism*; D005769:Gastrointestinal Motility; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006878:Hydroxides; D017665:Hydroxyl Radical; D008280:Magnetics; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002214:Capsules; D003432:Cross-Linking Reagents; D006878:Hydroxides; D017665:Hydroxyl Radical; D010100:Oxygen