Free radicals, antioxidant enzymes, and carcinogenesis

This review summarizes clinical studies in which glutathione was measured in tumor tissue from patients with brain, breast, gastrointestinal, gynecological, head and neck and lung cancer. Glutathione tends to be elevated in breast, ovarian, head and neck, and lung cancer and lower in brain and liver tumors compared to disease-free tissue. Cervical, colorectal, gastric, and esophageal cancers show both higher and lower levels of tumor glutathione. Some studies show an inverse relationship between patient survival and tumor glutathione. Based on this survey, we recommend approaches that may improve the clinical value of glutathione as a biomarker.

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Glutathione levels in human tumors.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840090324

Special article the glutathione S‐transferases: An update

Biotransformation or drug-metabolising enzymes have an important function in the detoxication of ingested toxic, carcinogenic, or tumour promoting compounds. Enzyme activity and isoenzyme composition of three biotransformation systems: glutathione S-transferase, uridine diphosphate-glucuronosyltransferase, and cytochrome P-450 were studied in normal small and large intestinal mucosa from three kidney donors. The activity of most drug-metabolising enzymes decreases slightly from proximal to distal small intestine, whereas in the mucosa of the large intestine a sharp fall in activity was observed. The isoenzyme composition for each of the three biotransformation systems changed from the small to the large intestine. Class Alpha glutathione S-transferases were not expressed in the colon, in contrast to the small intestine where both Alpha and Pi class isoenzymes are present. In addition, with monoclonal antibodies fewer protein bands for UDP-glucuronosyltransferases and cytochrome P-450 were detected in the colon. In the small intestine both isoforms P-450(4) and P-450(5) were present, whereas in the colon only reduced amounts of cytochrome P-450(4) could be visualised. For UDP-glucuronosyltransferase, 53 and 54 kDa proteins could be detected in the small intestine, but in the colon there was only weak staining of the 54 kDa band. In the normal human colon enzymes are less active and there are fewer isoenzymes present in the mucosa than in the small intestine. This implies a lower level of the detoxifying potential in the colon, which might be important in regard to the high rates of carcinogenesis in the colon.

https://gut.bmj.com/content/gutjnl/32/4/408.full.pdf

Biotransformation enzymes in human intestine: critical low levels in the colon?

The purpose of our study was to investigate the relationship between plasma and hair levels of Se, Zn, and Cu, and cancer. We selected a total of 66 patients affected by either breast (38) or lung (28) cancer. They entered into the study at the onset of disease, and before any chemical or radiotherapy. Controls were randomly selected among healthy people and were matched for sex, age, smoking habits, and residence. In the group of breast cancer, a significant decrease in hair Se was found compared to controls (p < 0.01), whereas plasma Se was only slightly decreased. No difference between cases and controls was detected in both hair and plasma levels of Zn and Cu. Subjects who developed lung cancer were significantly lower in hair Zn (p < 0.05) and Cu (p < 0.01) than controls, whereas there was no difference with regard to Se. In addition, plasma Cu of these patients was increased as compared to controls.

A case-control study on selenium, zinc, and copper in plasma and hair of subjects affected by breast and lung cancer

A high content of total glutathione and high activities of both GSH S-aryltransferase (CDNB) and GSH peroxidase were found in different segments of the human intestinal mucosa comparable to findings in human gastric mucosa. Intraindividual comparisons of tumorous and nontumorous tissue specimens in patients with adenocarcinomas of the colon and rectum revealed no marked differences in their glutathione content and enzyme activities except in the sigma, where we found significantly lower GSH concentrations and higher GSH S-aryltransferase activities in the carcinomatous tissue. γ-Glutamyl-transpeptidase activity, a marker of neoplastic cell growth in experimental hepatocarcinogenesis, did not differ between tumorous and nontumorous tissue areas. The presence and high activity of the GSH-dependent enzyme system in different segments of the human intestinal mucosa may reflect its role in the defense against toxic and putative carcinogenic xenobiotics entering the body via the gastrointestinal tract.

Glutathione and GSH-dependent enzymes in the tumorous and nontumorous mucosa of the human colon and rectum.

Der Gastrointestinaltrakt des Menschen ist einer Vielzahl potentiell toxischer und cancerogener Substanzen ausgesetzt. Diese konnen nach Bioaktivierung mit cellularen Makromolekulen kovalente Bindungen eingehen und so eine Zellschadigung hervorrufen. Glutathion und seine konjugierenden Enzyme binden elektrophile und radikalische Substanzen und schutzen dadurch die Zelle (4). Demgegenuber stehen carcinogenaktivierende, z.B. die Cytochrom-P-450-abhangigen Enzyme, welche u.a. Hydroxylierungs-, Epoxidierungs- und Demethylierungsreaktionen katalysieren (5). Angesichts der viel diskutierten Induktion des Colon-Carcinoms durch exogene Stoffe haben wir beide o.g. Enzymsysteme sowohl in gesunder menschlicher Dickdarmschleimhaut als auch in Dickdarmcarcinomen bestimmt.

M. Younes

Papers

Glutathione and GSH-dependent enzymes in the tumorous and nontumorous mucosa of the human colon and rectum.

Die Aktivität mikrosomaler und GSH-abhängiger Enzyme in der Schleimhaut des menschlichen Colons