Isolation of human colonic crypts for study of xenobiotics metabolism

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.