ELEVATED DNA-REPAIR CAPACITY IS ASSOCIATED WITH INTRINSIC RESISTANCE OF LUNG-CANCER TO CHEMOTHERAPY

Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemo therapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy, Th e mechanisms of this intrinsic resistance are unknown, This study was designed to investigate the role of DNA repair in intrinsic resistance of N-SCLC to cisplatin. A panel of primary N-SCLC cell cultures and e stablished cell lines were examined and compared to SCLC cell lines es tablished previously from untreated patients. The overall DNA repair c apacity was estimated by the ability of cells to reactivate the pRSV-C AT plasmid damaged by cisplatin (''host cell reactivation'' assay). Cy totoxicity was determined for cisplatin in vitro. N-SCLC cells were fo und to be significantly more resistant to cisplatin than SCLC cell lin es isolated from untreated patients (P < 0.01). The capacity of N-SCLC cells to reactivate pRSV-CAT plasmid damaged with cisplatin and trans fected into cells was higher in N-SCLC cells than in SCLC cells origin ating from patients who were untreated previously (P < 0.05). Correlat ion was also observed between chloramphenicol acetyltransferase activi ty and intrinsic resistance to cisplatin. However, no significant diff erence was observed between primary N-SCLC cultures and established ce ll lines. This study indicates that elevated DNA repair capacity is as sociated with drug resistance in lung cancer and suggests that modulat ion of DNA repair mechanisms), such as the incorporation of specific D NA repair inhibitor(s) in therapeutic regimens, may help to improve th erapeutic strategies of N-SCLC.