XENOBIOTIC-METABOLIZING ENZYME EXPRESSION IN COLONIC NEOPLASIA

The cytochrome P450, epoxide hydrolase, and glutathione S-transferase enzyme families play an important part in the metabolism of many carci nogens and anti-cancer drugs. The expression of two forms of cytochrom e P450 (P450 IA and P450 3A), epoxide hydrolase and of the alpha, mu, and pi forms of glutathione S-transferase in normal colon, colonic ade nomas, and adenocarcinoma of the colon were studied by immunohistochem istry. This allowed the precise cellular site and distribution of each enzyme to be determined. Expression of all the xenobiotic metabolisin g enzymes studied was almost wholly confined to the epithelial cells, whether in normal, adenoma or carcinoma samples, except that cytochrom e P450 3A was also identified in mast cells and glutathione S-transfer ase pi was also present in chronic inflammatory cells. Cytochrome P450 was present in only a small proportion of normal colon samples, where as epoxide hydrolase and glutathione S-transferase mu were identified in about half, and glutathione S-transferase alpha and pi in most norm al samples. By contrast all the enzyme forms studied were expressed in virtually all adenomas and in over half the carcinomas. These results suggest that cytochrome P450 IA and cytochrome P450 3A are more speci fic markers of colonic neoplasia than epoxide hydrolase or glutathione S-transferases alpha, mu, and pi.