title: DNA damage and repair in leukocytes of melanoma patients exposed in vitro to cisplatin.
abstract: Resistance to chemotherapeutic drugs can be an obstacle to a successful treatment of cancer patients in part associated with individual response and differences in the DNA repair system. The Comet assay is an informative test to investigate DNA damage and repair in cells in response to a variety of DNA-damaging agents, including chemotherapeutic drugs. The aim of this study was to assess leukocytes damage after in-vitro cisplatin treatment and DNA repair action using the Comet assay in 20 patients with melanoma and 20 cancer-free individuals. Leukocytes' DNA damage before and after cisplatin treatment, in three different concentrations, was analyzed. The DNA repair capability was investigated after 1-5 h of in-vitro cells growing without cisplatin. The Comet score of the patients' basal DNA damage was higher than that observed in controls, but the difference was not statistically significant (P=0.85). Although both groups had similar Comet scores to all cisplatin concentrations tested and the DNA repair times, the basal DNA damage (P<0.001) and cisplatin damages (P<0.005) were statistically lower than the different repair times investigated. Considering the progressive increase in the Comet score due to repair time, the negative results here observed could be associated with the reduced cell culture incubation that should be better evaluated. Considering the mutagenic action of cisplatin on tumor cells and the importance of individual DNA repair mechanisms in the chemotherapeutic melanoma treatment, the peripheral leukocytes could be particularly useful as a tool for DNA repair response identified by the Comet assay.
authors.affiliation: Department of Legal Medicine, Ethics, and Occupational Health, University of São Paulo, Rua Teodoro Sampaio 115, São Paulo, SP, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Shimabukuro
authors.forename: Cyro F
authors.initials: CF
authors.lastname: Neto
authors.forename: José A
authors.initials: JA
authors.lastname: Sanches
authors.forename: Gilka J F
authors.initials: GJ
authors.lastname: Gattás
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin