Drug-metabolizing enzyme expression in human normal, peritumoral and tumoral colorectal tissue samples.
In the present study, we investigated Phase I (cytochrome P450; DT-diaphorase, DTD) and Phase II (epoxide hydrolase, EH; glutathione-S-transferases, GSTs) enzymes in normal colon from patients without colorectal adenocarcinoma and in peritumoral and tumoral tissues from patients with colorectal adenocarcinoma. No significant changes in levels of cytochrome P450IIIA4 (the only P450 detectable in this tissue), EH, GSTs and DTD activity were found between normal and peritumoral tissues. In tumoral tissue, compared with peritumoral tissues, we observed significant decreases in cytochrome P450IIIA4 (-50%, P less than 0.002) and EH (-60%, P less than 0.03), no change in DTD activity and significant increases in GST pi (+40%, P less than 0.03) and total GST activity (+30%, P less than 0.01). The numerous changes observed in tumoral tissues suggest that variations in drug-metabolizing enzyme expression in colorectal adenomatous polyps could represent pretumoral markers. Moreover, a better understanding of the expression of these enzymes in tumoral tissues would help us to choose the most appropriate colon tumor cell lines for the testing of new anti-cancer drugs.
de Waziers
I
I
INSERM U75, CHU-Necker, Paris, France.
Cugnenc
P H
PH
Berger
A
A
Leroux
J P
JP
Beaune
P H
PH
D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004851:Epoxide Hydrolases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D011808:Quinone Reductases / Q000378:metabolism; D012016:Reference Values
D003577:Cytochrome P-450 Enzyme System; D011808:Quinone Reductases; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases