1-(1-glycero)dodeca-1-3-5-7-9-pentaene and 4-hydroxy-2-nonenal

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.

Topics: Aldehydes; Animals; Capsules; Cross-Linking Reagents; Gastrointestinal Transit; Glutaral; Guanosine; Magnetics; Male; Mutagens; Polyenes; Polyethyleneimine; Polyethylenes; Rats; Rats, Inbred F344