REPAIR OF DNA DAMAGED BY THE ANTICANCER DRUG CIS-PLATINUM IN HUMAN LUNG CANCER CELL LINES

Worldwide lung cancer is the main reason for cancer death among men and the second reason for cancer death among women. The anticancer drug cis-platinum is the most frequent agent used for chemotherapy of non-small-cell lung cancer (NSCLC). However, less than 30% of NSCLC patients respond to cis-platinum. Nucleotide excision repair (NER) of DNA appears to be a major mechanism of cis-platinum resistance. It was established that the efficiency of NER of certain types of DNA damage was regulated by the p53 tumour suppressor protein and in more than half of NSCLC tumours the p53 gene was mutated. For this reason it is important to establish whether p53 status affects the ability of the cells to remove the cytotoxic lesions induced by chemotherapeutic drugs such as cis-platinum. We compared the intrinsic level of DNA repair efficiency of cis-platinum damages in two NSCLC lines, A549 (p53 +/+) and H1299 (p53 -/-), in view of their p53 status. Cells with wild type p53 showed higher repair potential in the early stages of the process while after 24 h the p53 mutant cells registered higher levels of reactivation in Host-Cell Reactivation assay (HCR).