Oesophageal carcinoma is a common form of cancer in developing countries, especially in the Caspian littoral and northern China. In contrast, it has a much lower incidence in Japan, the U.S.A. and western Europe. Certainly in the case of squamous cell oesophageal carcinoma, dietary composition, smoking, alcohol and exposure to nitrosamines are major risk factors that may partly explain the disease's geographical distribution. The prognosis for oesophageal carcinoma is generally poor, due to the high incidence of distant metastasis and local recurrence. Combination treatment with both cisplatin and 5-fluorouracil is the most common chemotherapy regime used. We have carried out a detailed study of sensitivity of two oesophageal cell lines: OC1 cells from a squamous carcinoma of a male patient, and OC2, a squamous carcinoma obtained from a female patient. Both cell lines are sensitive to Vinca alkaloids and doxorubicin, while being quite resistant to alkylating agents such as cisplatin and l,3-bis-(2-chloroethyl)-1-nitrosourea. This pattern of resistance suggests a possible role for glutathione S-transferase (GST) and/or glutathione (GSH) in resistance, and would seem to exclude the multidrug resistance phenotype. Both cell lines possess mainly Pi-class GSTs, and have distinct levels of GSH, with OC2 possessing some 25 % of the level of OC1 cells. Effects of a variety of modulating agents on the pattern of resistance, such as the GSH depleter, buthionine sulphoximine, and the GST inhibitor, ethacrynic acid, were determined. An unexpected observation was that ethacrynic acid appears to increase the level of GSH in both cell lines.
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Conference Article|
February 01 2000
Chemical modulation of chemotherapy resistance in cultured oesophageal carcinoma cells
D. Sheehan;
D. Sheehan
1
1Department of Biochemistry, University College Cork, Lee Maltings Prospect Row, Mardyke, Cork, Ireland
1To whom correspondence should be addressed.
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G. Meade
G. Meade
1Department of Biochemistry, University College Cork, Lee Maltings Prospect Row, Mardyke, Cork, Ireland
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Publisher: Portland Press Ltd
Received:
September 09 1999
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2000 Biochemical Society
2000
Biochem Soc Trans (2000) 28 (2): 27–32.
Article history
Received:
September 09 1999
Citation
D. Sheehan, G. Meade; Chemical modulation of chemotherapy resistance in cultured oesophageal carcinoma cells. Biochem Soc Trans 1 February 2000; 28 (2): 27–32. doi: https://doi.org/10.1042/bst0280027
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