Presence of endogenous cross-linking/bifunctional agents in gastrointestinal cavity as detected by transit of magnetic PEI microcapsules

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Abstract
After gastrointestinal (GI) transit through rats, semipermeable bifunctional microcapsules containing polyethyleneimine(PEI) as a DNA-simulating nucleophilic target showed physicocheimical alterations consistent with PFI 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 mem brane 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 radlolabel and a colorimetric label, and were attributable to both stomach and caecal sourcesby microcapsule recovery from the excised GI tract. By acid treatment of recoveredmlcrocapsules, 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 treat ment with 10 μmol glutaraldehyde but this seems a severe underestimate due both to known limited trapping of GI electrophiles by limited quantity of microcapsules and demonstratedlow 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.

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