Magnetic microcapsules suitable for in vivo carcinogen-trapping and facile recovery are being developed for direct monitoring of the gastro-intestinal tract. The proposal concerns developments (beyond the preliminary feasibility study) and applications of a system, believed to be needed for biochemical epidemiology, to rapidly detect colorectal carcinogenesis risks that vary both interindividually and with choice of diet. The long-term objective is to develop several microencapsulated trapping agents (and establish the relevant, newly-available highly sensitive analytical methods) for eventual human use. In the next two years, this proposal has three specific aims: a) complete preparation of 3 types* of magnetic microcapsule by chemical attachment of guanosine, ellagic acid and piperazine target moieties to presently available microencapsulated polyethyleneimine; b) demonstrate effectiveness in rodents treated with radioactive carcinogens, or with nitrite in drinking water, for which appropriate assay techniques using radioactive counting and TEA already exist; c) detect (using 32P post-labeling and other extremely sensitive methods) both the given carcinogens and as-yet uncharacterized seemingly-genetically-active species that the trapping species should encounter. For rodent experimentation, it is intended to use 14C-benzo(a)pyrene and 14C-dimethylhydrazine in mouse species (of opposite susceptibilities to these substances) and compare effectiveness of the traps and the effects of dietary variation (fat, fibre, bile acids) so as to produce individual response profiles. Relevant host characteristics will be evident in the extent of activation of carcinogens, or deconjugation of carcinogen conjugates, or production of endogenous N-nitrosation conditions, and also utilised since the microcapsules envisaged will not contain activation or deconjugation systems. Providing the microcapsule trapping system in both effective and without harm, extension to a third year for human tests may be proposed later. *Guanosine, ellagic acid and piperazine selected as being respectively the most reactive nucleic acid base, a catalytic trap for activated PAH, and the most readily nitrosatable base, for competition with other substances in the GI tract or its contents.
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