DETECTION OF MULTIPLE RESISTANCE MECHANISMS IN UNTREATED HUMAN LUNG-CANCER

Background: The aim of the study was to analyze whether or not a short -term test is able to detect drug resistance of tumors caused by vario us resistance mechanisms. Materials and Methods: The drug resistance o f 94 human non-small-cell lung carcinomas was measured using an in vit ro short-term test. Its basic feature is measurement of changes in the incorporation of radioactive nucleic acid precursors into cell suspen sions made from fresh tumor biopsies after addition of doxorubicin. Th e expression of P-glycoprotein, glutathione S-transferase pi, topoisom erase II, catalase, thymidylate synthase, and metallothionein was asse ssed immunohistochemically using alcohol-fixed paraffin-embedded secti ons. Results: Significant correlations were found between the results of the short-term test and the increased expression of P-glycoprotein, glutathione S-transferase pi, thymidylate synthase, and metallothione in. In 44% of the doxorubicin-resistant tumors all four resistance-rel ated proteins were detected; in 85% of the doxorubicin-resistant tumor s more than one of these proteins were detected. The probability of de tecting resistance by an in vitro short-term test increases with the n umber of resistance-related proteins in the tumor. Conclusion: The in vitro short-term test may thus help to detect different resistance mec hanisms.