title: DNA crosslinks, DNA damage and repair in peripheral blood lymphocytes of non-small cell lung cancer patients treated with platinum derivatives.
abstract: Lung cancer is the leading cause of cancer-related mortality in the world. Chemotherapy has been the mainstay of treatment for advanced non-small cell lung cancer (NSCLC) and platinum-based derivatives have been shown to improve overall survival. The aim of the present study was to investigate the DNA damage [single strand breaks (SSBs) and DNA crosslinks] and DNA repair in peripheral blood lymphocytes in patients with NSCLC treated with platinum derivatives using modified comet assay. Twenty patients in the final (4th) stage of NSCLC and 10 age-corresponding healthy controls participated in the study. Alkaline comet assay was performed according to the appropriate protocol. The DNA base excision repair (BER) activity of the controls was significantly higher compared to that of cancer patients, and the activity of DNA nucleotide excision repair (NER) was almost at the same level both in controls and patients. We observed changes in the amount of SSBs and DNA crosslinks during the course of chemotherapy. We found a significantly higher level of SSBs immediately after administration of chemotherapy. Similarly, we found the highest incidence of DNA crosslinks immediately or 1 day after chemotherapy (compared to measurement before chemotherapy). Moreover, we compared the levels of DNA repair in patients who survived chemotherapy with those in patients who died in the course of chemotherapy: the activity of BER was higher in the case of surviving patients, while the levels of NER were essentially the same. The data arising from the present study confirm the findings of other studies dealing with DNA damage and repair in cancer patients treated with chemotherapy. Moreover, our results indicated that despite the fact that cisplatin-DNA adducts are removed by the NER pathway, BER may also play a role in the clinical status of patients and their survival.
authors.affiliation: Department of Biological and Medical sciences, Faculty of Pharmacy, Charles University in Prague, Hradec Králové, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Fikrova
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stetina
authors.forename: Michal
authors.initials: M
authors.lastname: Hrnciarik
authors.forename: Dana
authors.initials: D
authors.lastname: Hrnciarikova
authors.forename: Miloslav
authors.initials: M
authors.lastname: Hronek
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Zadak
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use*; D020552:Comet Assay; D018736:DNA Adducts / Q000235:genetics*; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; C057270:cisplatin-DNA adduct; D002945:Cisplatin