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Isolation of human colonic crypts for study of xenobiotics metabolism
M Schwenk1, P Déchelotte, T Riemenschneider
1Abteilung Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Federal Republic of Germany.
Abstract:
Methods allowing study of human colonic drug and carcinogen metabolism in intact epithelial preparations in vitro are needed. We describe an isolation method yielding intact colonic crypts with well-maintained ultrastructural integrity and good viability parameters. The crypt preparations obtained with this method were used to study phase I and II drug biotransformation. The colonic crypts demethylated aminopyrine and nitrosodimethylamine slowly, but the colonic carcinogen dimethylhydrazine at a higher rate. The phenolic compounds estrone, 17 beta-estradiol, and 1-naphthol were readily conjugated. In conclusion, the present method yields preparations well suited for further investigation of the role of human colonic biotransformation in carcinogenesis and drug pharmacokinetics.