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Parallel assessment of glutathione‐based detoxifying enzymes, O 6 ‐alkylguanine‐dna alkyltransferase and P‐glycoprotein as indicators of drug resistance in tumor and normal lung of patients with lung cancer
Author(s) -
OberliSchrämml Aurelia E.,
Joncourt Franziska,
Stadler Markus,
Altermatt HansJorg,
Buser Kathrin,
Ris HansBeat,
Schmid Ulrico,
Cerny Thomas
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910590509
Subject(s) - glutathione , lung cancer , glutathione peroxidase , cancer research , biology , glutathione s transferase , p glycoprotein , pathology , microbiology and biotechnology , medicine , enzyme , drug resistance , biochemistry , multiple drug resistance , genetics
The levels of several potential indicators of drug resistance were measured in tumor and corresponding normal tissue of 55 untreated patients with lung cancer. The resistance parameters include glutathione (GSH) level, activities of the enzymes glutathione transferase (GST), glutathione peroxidase (GPx) and O 6 ‐alkylguanine‐DNA alkyltransferase (ATase), as well as expression of P‐glycoprotein (Pgp). Median values of GSH, GST and GPx were significantly higher in tumor than in normal tissue of non‐small‐cell lung cancer (NSCLC) or of small‐cell lung cancer (SCLC), whereas ATase was elevated in tumor tissue of NSCLC only. Pgp expression as determined by Western blotting was significantly lower in tumor than in normal tissue of NSCLC. Resistance‐parameter expression did not correlate with stage of disease or age of the patients. We found a negative correlation between smoking intensity and GSH level in normal tissue. Our findings indicate that the fundamental differences in chemo‐sensitivity between SCLC and NSCLC cannot be explained by differences in the GSH‐system or in the expression of Pgp. However, the level of ATase activity may be one of the factors responsible for the difference in chemosensitivity.