title: Presence of endogenous cross-linking/bifunctional agents in gastrointestinal cavity as detected by transit of magnetic PEI microcapsules.
abstract: After gastrointestinal (GI) transit through rats, semipermeable bifunctional microcapsules containing polyethyleneimine (PEI) as a DNA-stimulating nucleophilic target showed physiochemical alterations consistent with PEI amine functions being intermolecularly cross-linked as by bifunctional agents. Such cross-linking both within the membrane and inside the microcapsules between core PEI and membrane PEI was simulated in vitro by glutaraldehyde, guanosine dialdehyde, 4-hydroxynonenal and fecapentaene-12, the latter two agents being known to form cyclic adducts or cross-links on DNA. These in vivo effects were demonstrated using both a radiolabel and a colorimetric label, and were attributable to both stomach and caecal sources by microcapsule recovery from the excised GI tract. By acid treatment of recovered microcapsules, cross-links formed in stomach and caecum were found to be respectively acid sensitive and acid resistant. The cross-linking effects observed were equivalent to treatment with 10 mumols glutaraldehyde but this seems a severe underestimate due both to known limited trapping of GI electrophiles by limited quantity of microcapsules and demonstrated low efficiency by glutaraldehyde in forming cross-links versus amine modifications. These results demonstrate that there are substantial concentrations of endogenous, membrane-penetrating, cross-linking/bifunctional agents in the GI tract which have significance due to the potent DNA-damaging and carcinogenic properties of such agents as a class.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Ellul
authors.forename: A
authors.initials: A
authors.lastname: Povey
authors.forename: I K
authors.initials: IK
authors.lastname: O'Neill
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D002214:Capsules; D003432:Cross-Linking Reagents / Q000032:analysis*; D005772:Gastrointestinal Transit; D005976:Glutaral / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D008280:Magnetics; D008297:Male; D009153:Mutagens / Q000494:pharmacology; D011090:Polyenes / Q000494:pharmacology; D011094:Polyethyleneimine; D011095:Polyethylenes; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000447:Aldehydes; D002214:Capsules; D003432:Cross-Linking Reagents; D009153:Mutagens; D011090:Polyenes; D011095:Polyethylenes; D006151:Guanosine; C021691:guanosine dialdehyde; C037357:1-(1-glycero)dodeca-1,3,5,7,9-pentaene; D011094:Polyethyleneimine; C027576:4-hydroxy-2-nonenal; D005976:Glutaral