REACTIVE MICROCAPSULES FOR DETECTION OF CARCINOGEN SOURCES IN THE GUT

Entrapment within the gastrointestinal tract of reactive carcinogens and DNA-damaging agents was achieved by use of novel magnetically-retrievable semi-permeable microcapsules. Investigation of colorectal cancer aetiology cannot be based on faecally-excreted agents, and this in situ trapping provides the only means for monitoring internal exposures. These microcapsules were initially prepared from polyethyleneimine with a polyamide membrane so as to resist microfloral and enzymatic damage, and are shown to entrap metabolites of radioactive carcinogens with substantial influences of human dietary components that were consistent with previous epidemiological results on diet-related cancer risks for the human colon. These microcapsules were subsequently modified by covalent attachment of target moieties, and used to reveal several types of endogenous agent of carcinogenic significance. These included cross-linking and nitrosating agents, precursors of reactive oxygen species, and carcinogens having planar molecular structure. Preliminary studies in man have been undertaken and have showed diet-dependent effects. The aim of this work is to identify DNA-damaging agents and their dietary sources, and preliminary work with modified microcapsules and in volunteers consuming controlled diets indicates this to be feasible. Such microcapsules could in principle be used for many other types of applications beyond the scope of this present work.