title: Combined gamma-irradiation and subsequent cisplatin treatment in human squamous carcinoma cell lines sensitive and resistant to cisplatin.
abstract: OBJECTIVE
  To investigate the effects of combined radiation and subsequent cisplatin treatment on the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP.
  
  
  METHODS
  SCC-25 and SCC-25/CP cells were treated with various gamma-ray doses (5 cGy-7 Gy) followed 60 min later by cisplatin treatment and subsequently assayed for survival using a conventional colony assay. For SCC-25, the subsequent cisplatin treatment was 0.1, 1, 10 and 20 microM for 1 h. For the more cisplatin-resistant SCC-25/CP cells, the subsequent cisplatin treatment was 10 and 50 microM for 1 h.
  
  
  RESULTS
  The cisplatin-resistant SCC-25/CP cells were not cross-resistant to gamma-irradiation. Subsequent treatment with an LD50 concentration of cisplatin (10 and 50 microM for SCC-25 and SCC-25/CP, respectively) resulted in radiosensitization for SCC-25/CP but not for SCC-25 cells. Gamma-irradiation of SCC-25/CP cells followed by treatment with 10 and 50 microM cisplatin for 1 h resulted in radiation survival curves displaying a significant low-dose hypersensitive region followed by increased radioresistance at higher doses. A total of 10 microM cisplatin resulted in radiosensitization confined to the low-dose region (0.05 and 0.25 Gy), whereas the higher cisplatin treatment of 50 microM resulted in the appearance of a hypersensitive region together with a reduction of the increased radioresistance region. In contrast, cisplatin treatment (0.1, 1, 10 and 20 microM for 1 h) of SCC-25 cells had no significant effect on survival following 2.5 or 7.0 Gy and actually resulted in an increased low-dose radiation survival (0.05, 0.25 and 1 Gy) when survival was corrected for cisplatin treatment (p<0.01 for all cisplatin concentrations tested).
  
  
  CONCLUSIONS
  The significant radiosensitization for SCC-25/CP given subsequent treatment with 50 microM cisplatin indicates cisplatin can inhibit the increased radioresistance response in SCC-25/CP cells. In contrast, the subsequent cisplatin treatment of SCC-25 cells can enhance their survival following low radiation doses.
authors.affiliation: Department of Physics and Astronomy, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Caney
authors.forename: G
authors.initials: G
authors.lastname: Singh
authors.forename: H
authors.initials: H
authors.lastname: Lukka
authors.forename: A J
authors.initials: AJ
authors.lastname: Rainbow
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects*; D005720:Gamma Rays / Q000627:therapeutic use; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin