Alteration of cytochrome P-450 and glutathione S-transferase activity in normal and malignant human stomach.
Cytochrome P-450 and glutathione S-transferase (GST) activities were investigated in stomach tumor and tumor-adjacent tissues of patients (n = 211) with gastric adenocarcinoma, and in the stomach tissues of unaffected individuals (normal tissues, n = 113). A significant reduction in total cytochrome P-450 activity was observed in tumor and tumor-adjacent tissues versus normal stomach. In all cases, cytochrome P-450 activity was significantly higher in males than in females. In the case of smokers, cytochrome P-450 activity was 1.8-fold higher in tumor-adjacent than in corresponding tumor tissues, but no difference was observed in nonsmokers. Patients had significantly lower GST activity in tumor and tumor-adjacent tissues compared to normal tissues. Smokers showed lower GST activity in both tumor and tumor-adjacent tissues compared to nonsmokers. In addition, GST activity was significantly lower in tissues positive for Helicobacter pylori infection than in H. pylori-negative tissues. However, the frequency of H. pylori infection was higher in tumor-adjacent (69%) than in tumor (45%) or normal tissues (44%). Our data suggest that diminished GST enzymes activity and increased cytochrome P-450 activity in normal and tumor-adjacent tissues might be due to the direct effect of the H. pylori infection and cigarette smoking, respectively. Data indicate that alterations in the activities of cytochrome P450 and GST may in part be associated with an increased risk for gastric cancer.
Kim
Hyung Sik
HS
Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, Jangjun-dong, Gumjung-gu, Pusan.
Kwack
Seung Jun
SJ
Lee
Byung Mu
BM
D000230:Adenocarcinoma / Q000201:enzymology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013270:Stomach / Q000201:enzymology*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000209:etiology
D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase