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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA039417-01
Application #
3178351
Study Section
(SSS)
Project Start
1985-09-30
Project End
1987-09-29
Budget Start
1985-09-30
Budget End
1986-09-29
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
International Agency for Research on Cancer
Department
Type
DUNS #
279551881
City
Lyon
State
Country
France
Zip Code
69372
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Alexakis, T; Boadi, D K; Quong, D et al. (1995) Microencapsulation of DNA within alginate microspheres and crosslinked chitosan membranes for in vivo application. Appl Biochem Biotechnol 50:93-106
O'Neill, I; Bingham, S; Ellul, A et al. (1993) Magnetic microcapsule exploration in the gastrointestinal cavity of the origins of colorectal cancer-associated DNA-damaging agents in the human diet. Environ Health Perspect 99:161-7
O'Neill, I; Ridgway, O; Ellul, A et al. (1993) Gastrointestinal monitoring of DNA-damaging agents with magnetic microcapsules. Mutat Res 290:127-38
Rumney, C J; Rowland, I R; Coutts, T M et al. (1993) Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats. Carcinogenesis 14:79-84
O'Neill, I (1993) Reactive microcapsules for detection of carcinogen sources in the gut. J Microencapsul 10:283-308
Bingham, S A; Ellul, A; Cummings, J H et al. (1992) Novel detection by magnetic microcapsules in the human gastrointestinal tract of cross-linking agents and diet-dependent reactive oxygen species. Carcinogenesis 13:683-90
O'Neill, I; Ohgaki, H; Ellul, A et al. (1992) Entrapment by magnetic microcapsules of the protein pyrolysates IQ, PhIP and Glu-P-1, and alteration of IQ metabolite exposure within the rat gastrointestinal tract by risk-modulating components of the human diet. Carcinogenesis 13:2353-9
O'Neill, I K; Goldberg, M T; el Ghissassi, F et al. (1991) Dietary fibre, fat and beef modulation of colonic nuclear aberrations and microcapsule-trapped gastrointestinal metabolites of benzo[a]pyrene-treated C57/B6 mice consuming human diets. Carcinogenesis 12:175-80
Ellul, A; Povey, A; O'Neill, I K (1990) Presence of endogenous cross-linking/bifunctional agents in gastrointestinal cavity as detected by transit of magnetic PEI microcapsules. Carcinogenesis 11:1577-82

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