Identification and elimination of dietary cancer risk factors is the long-term objective of applying-non-invasive magnetically-retrievable semi-permeable microencapsulated targets for gastrointestinal (GI) trapping of DNA-damaging agents, with their eventual use for dosimetry in linking dietary components with alterations to mucosal biomarkers. Microcapsule utility and related major modulations by human diets of carcinogen action have been demonstrated, while microcapsule structural advances and ethical acceptance have been achieved. The proposed continuation is to precede/complement extensive human use (1922) and is a balance of 1) application of existing microcapsule systems in understanding how human diets modulate GI cancer risk by altering exposure of target organs and 2) testing new microcapsule targets and introducing gene-related targets for more specifically monitoring causes of critical biological damage. This is the sole method of GI biomonitoring and the following specific aims (encompassing actually feasible techniques and biological meaningfulness of data) are: a) to exploit microcapsule of two trapping types with physico-chemical assays namely: i) a synthetic, deoxyguanosine (dG)-simulating target for mass spectral and HPLC identification of endogenous reactive electrophiles, ii) PEI as an efficient N-nitrosation substrate; B) to clarify significance of endogenous GI agents already found by 3 other microcapsule end-points i.e. endogenous bifunctional alkylating (cross-linking) agents, reduced oxygen species e.g. hydroxyl radicals, and mutagens with planar structures; C) to develop and test microcapsule structures permitting inclusion of intact ras/p53 oligo/poly-nucleotide sequences; D) selected applications in rodents with already used human diets (and protein pyrolysates) including elucidation of modulating factors for minimizing mucosal DNA damage. The latter includes preliminary studies on effects of anti-carcinogens, and of microflora vs host metabolism (controlling hosp phenotypes). This battery of targets appears to be needed to cover most aspects of multi-stage carcinogenesis in several GI regions, and many suspected etiological agents. In keeping with progress and its potential importance, this multi-disciplinary study involves 8 recognized extra- mural experts and their facilities; it is designed to interface directly with human studies, producing the same systems and information needed for use in molecular epidemiology.
Showing the most recent 10 out of 23 publications
