Follow-up Cancer Cell Lines Established from One Patient during Clinical Resistance Mechanisms in Three Human Small Cell Lung

Mechanisms for resistance were studied in three classic type, human small cell lung cancer cell lines, (.!(,,, (.I.(',„,and <;i.<',.i, that were established from one patient during clinical follow-up. Clinically the tumor changed from sensitive (<;!,(,,) to completely resistant to (chemo)therapy ((il.(.',,,) during this period. The stain with JSB-1 anti body, detecting the M, 170,000 multidrug resistance associated glycoprotein, was most pronounced in ( i l .("„, and absent in ( ; I ( ,.,. Intracellular Adriamycin (Adr) concentrations were decreased in <•!(,„ and GLCi, versus (il.(',,. Glutathione levels were 12.9,15.5, and 16.6 «ig/mgprotein; total sulfhydryl groups were 36.5, 45.7, and 48.8 ¿ig/mgprotein; and glutathione 5-transferase activity was 13, 29, and 43 nmol l-chloro-2,4dinitrobenzene/min/mg protein for (il.(',,, (il.( '„„ and (il.( ',.>.respec tively. Incubation with DL-buthionine-5,£-suIfoximine increased Adr and cisplatin induced cytotoxicity, whereas X-ray induced cytotoxicity re mained the same. Catalase activity increased from 0.88 to 1.73 to 3.83 Minol11?()_,/min/ni« protein in, respectively, GLC(4, (il.('„„ and (il ,(',.)• Compared to (¿l.(,4 and (;!.(,,„Adr induced a higher amount of DNA strand breaks in G!,(,,,. In none of the three cell lines could Adr induced DNA strand breaks be repaired. X-ray induced a comparable amount of DNA strand breaks in all three cell lines but all cell lines were capable of repairing the X-ray induced DNA strand breaks within 90 min. It is concluded that a number of different mechanisms are operative and that some but not all of the observed changes in mechanisms for drug resistance in these lines correlate with the clinical data.