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Cytochrome P450 activity and distribution in the human colon mucosa
Author(s) -
Stralka Daniel J.,
Strobel Henry W.
Publication year - 1989
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19891115)64:10<2111::aid-cncr2820641023>3.0.co;2-s
Subject(s) - carcinogen , microsome , cytochrome p450 , in vitro , oxidase test , enzyme , intestinal mucosa , distribution (mathematics) , biochemistry , chemistry , medicine , mathematical analysis , mathematics
Enzymatic activity associated with the mixed‐function oxidase system was determined in microsomes prepared from the mucosal cells extracted from normal human colons. A high activity toward nitrogen oxidation reactions was observed. 1,2‐Dimethylhydrazine, a colon‐specific carcinogen, was metabolized at a higher rate in vitro by human colon microsomes as compared with the rat, and exhibited a k m tenfold lower, 1.03 mmol/l versus 9.68 mmol/l, respectively. This activity was inhibited by classic cytochrome P450 inhibitors; 70% inhibition was achieved using 70 mmol/l metyrapone (2‐methyl‐1,2‐di‐3‐pyridyl‐1‐propanone), 20 mmol/l; SKF‐525A (diethylaminoethyl‐2,‐2‐diphenylvalerate HCl), or 350 μmol/l n‐octylamine. These data suggest the presence of a stable, active mixed‐function oxidase system in the human colon mucosa which has a preferential activity toward nitrogenous compounds and provides a mechanism for the activation of carcinogens. Its distribution in the colon appears to parallel the reported incidence of human colonic carcinomas.