GASTROINTESTINAL MONITORING OF DNA-DAMAGING AGENTS WITH MAGNETIC MICROCAPSULES

Semi-permeable, magnetically recoverable, reactive microcapsules of several types were developed for gastrointestinal (GI) monitoring of several kinds of DNA-damaging agents in relation to (i) systematic dietary variations designed to discriminate the GI effects of food components known to modulate colorectal cancer risk, and (ii) then thereby to achieve the identification of a range of endogenous agents and their dietary sources. These microcapsules contained as targets either amino functions (for alkylating agents), (CH3)-C-14 functions (to detect cross-linking agents and reactive oxygen species precursors), or a copper porphyrin (for carcinogens having planar molecular structure). Other microcapsules had a cleavable target based on guanine, which is shown to trap endogenous agents and a [C-14]BaP metabolites in male F344 rats consuming a putative high-risk diet (high fat, high meat, low fibre non-starch polysaccharide (NSP)), but not significantly when consuming the contrasting low-risk diet. Detailed investigations of the action of fibre NSP and fat showed that increased intake from low to high levels of the British diet range enhanced or decreased several carcinogenesis-relevant end-points more than two-fold. Detection of these disproportionately large effects on microcapsule trapping, hepatic DNA adducts from endogenous agents, colorectal mucosal cell mitoses/micronuclei, endogenous cross-linking agents, and gut microfloral enzyme activities (a) are consistent with epidemiological data on the importance of these components and (b) provide the basis for establishing with microcapsules some potential dietary preventive measures in volunteers.