Human colonocyte detoxification (original) (raw)

Human colonocyte detoxification

WILLIAM E W ROEDIGER,
WENDY BABIDGE
Colorectal Unit and Cell Physiology Laboratory, Department of Surgery of the University of Adelaide at The Queen Elizabeth Hospital, Adelaide, SA 5011, Australia
Associate Professor Roediger.

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Detoxification or biotransformation of drugs and xenobiotics are usually linked with liver metabolism, yet colonocytes of the gastrointestinal tract have an equal capacity to mediate these processes.1 ,2 This brief overview specifically discusses the ability of human colonocytes, but not other tissues, to detoxify chemical agents and relates pertinent findings to ulcerative colitis and some aspects of colon cancer. Failure to detoxify, leading to epithelial cell damage, or an exaggerated capacity to biotransform, leading to carcinogen formation in colonocytes, have been the main implications in disease processes.

In general, two categories of detoxification processes are recognised (table 1)3 ,4: phase I reactions concern oxidation, reduction and hydrolysis within the cytosol, and phase 2 reactions require ATP and concern conjugation with a donor substrate synthesised in the cell. Both reactions need enzymes such as oxidoreductases, hydrolases, transferases, and lyases. Amongst these may be subclasses, genetic polymorphism and variability of enzyme activity in organs and along the gastrointestinal tract. Particularly, differences in enzyme activity in the proximal and distal colon may occur.5 ,6

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Table 1

Detoxification and biotransformation reactions found in human colonocytes

Biochemists, pharmacologists, toxicologists, molecular biologists, geneticists, oncologists, and gastroenterologists are involved in this field of study, from each of which information is now drawn together. Many new toxicological advances made with liver and lung tissues still have to be applied to colonocytes and would be a fruitful area of future research. The subject of clinical gastrointestinal toxicology7 makes it possible to bridge a gap between colonic disease, genetics and the ability to detect initiating or promoting factors in ulcerative colitis and colon cancer.

Cytoplasmic oxidases and reductases

Cytochrome P-450 are a superfamily of haem containing mono-oxygenases8 acting in the metabolism of foreign compounds, as well as synthesis of steroids and bile components. The P-450 superfamily …