Abstract
Oxyradicals are involved in multiple mutational events and can contribute to the conversion of healthy cells to cancer cells. Glutathione (GSH) and the GSH-replenishing enzymes keep the antioxidant status of normal cells at a level where they can avert oxyradical derived mutations. The aim of this study was to determine whether in cancer cells the GSH-replenishing, GSH antioxidant and GSH-depleting enzymes were not at appropriate levels and therefore not able to protect cancer cells adequately against oxyradical-induced mutations. Cancer of the oesophagus was chosen since it is the most common gastrointestinal malignancy in South African Blacks. Biopsies and blood from 31 patients with cancer of the oesophagus and 29 non-cancer patients were assessed for these enzymes. The mean activity of the antioxidant and depleting enzyme GSH-peroxidase was elevated significantly by twofold in the cancer tissue compared to normal tissue. However, the activity of the replenishing enzyme GSSG-reductase and the level of the depleting enzyme GSH-s-transferase P1-isoenzyme were significantly reduced by 23% and 33% respectively. As in a previous paper we found that GSH was depleted and γ-glutamine transpeptidase was diminished in oesophageal cancer. There can be two reasons for GSH depletion. Firstly, elevated GSH–peroxidase will use more GSH in an attempt to cope with the excessive production of oxyradicals as revealed by elevated lipid peroxidation; this was, as shown by us before, elevated sixfold in oesophageal cancer. Secondly, if little replenishment of GSH occurred the level of GSH would become lower. This was confirmed by our findings that the activities of the replenishing enzymes were significantly diminished in oesophageal cancer tissue. Contrary to what was expected, the other depleting enzyme GSH-s-transferase P1 was not elevated in cancer tissue but was significantly lower. However, in the blood of the same patients it was significantly elevated. An explanation for this phenomenon is that, although the production of GST-P1 was enhanced in cancer, it did not show because it was rapidly extruded into the blood by an unknown mechanism operational only in cancer cells.
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Levy, R., Oosthuizen, M., Degiannis, E. et al. Glutathione-linked enzymes in benign and malignant oesophageal tissue. Br J Cancer 80, 32–37 (1999). https://doi.org/10.1038/sj.bjc.6690317
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DOI: https://doi.org/10.1038/sj.bjc.6690317
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