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Glutathione concentrations and glutathione S-transferase activity in human colonic neoplasms
R N Butler1, W J Butler, Z Moraby
1Department of Gastroenterology, Queen Elizabeth Hospital, Woodville, Australia.
Abstract:
Tissue concentrations of glutathione (GSH) and the activity of glutathione S-transferases (GST) are relevant to the inactivation of a variety of xenobiotics including carcinogens and anti-neoplastic drugs. In this study, GSH concentrations and GST activity were determined in 25 adenomatous polyps removed at colonoscopy, and in cancer and uninvolved 'normal' mucosa from 58 operative specimens containing colon cancer. We also examined the relationship between GSH concentrations, GST activity and rates of cell proliferation as assessed by flow cytometry. Concentrations of GSH were significantly higher in adenomas (P = 0.001) and cancer (P = 0.001) than in uninvolved mucosa while GST activity was significantly higher in cancer (P = 0.007). There was a positive relationship between GSH concentrations and GST activity in adenomas (P = 0.001) but not in uninvolved mucosa (P = 0.06) or cancer (P = 0.4). Concentrations of GSH and GST activity were independent of results from flow cytometry. The higher concentrations of GSH in colonic neoplasms and the raised activity of GST in cancer may contribute to their resistance to anti-neoplastic drugs.
Insights
Colorectal neoplasms like adenomas and cancers show higher glutathione (GSH) levels. Glutathione S-transferase (GST) activity is elevated in colon cancer, potentially contributing to drug resistance.
Area of Science:
- Biochemistry
- Oncology
- Gastroenterology
Background:
- Glutathione (GSH) and glutathione S-transferases (GST) are crucial for detoxifying xenobiotics, including carcinogens and anti-cancer drugs.
- Understanding GSH and GST levels in colorectal tissues is vital for predicting treatment response.
Purpose of the Study:
- To quantify tissue concentrations of GSH and GST activity in colorectal adenomas, cancers, and normal mucosa.
- To investigate the correlation between GSH, GST activity, and cell proliferation rates in these tissues.
Main Methods:
- Analysis of GSH concentrations and GST activity in 25 adenomatous polyps and 58 colon cancer specimens (including cancer and normal mucosa).
- Cell proliferation rates assessed using flow cytometry.
- Statistical analysis to determine significance and relationships between variables.
Main Results:
- GSH concentrations were significantly higher in adenomas and cancers compared to normal mucosa (P = 0.001).
- GST activity was significantly elevated in colon cancer tissue (P = 0.007).
- A positive correlation between GSH and GST was observed in adenomas (P = 0.001), but not in normal mucosa or cancer. GSH and GST levels were independent of cell proliferation rates.
Conclusions:
- Elevated GSH in colonic neoplasms and increased GST activity in colon cancer may confer resistance to anti-neoplastic drugs.
- These findings highlight potential mechanisms for drug resistance in colorectal cancer.