title: In vitro interaction of high-LET heavy-ion irradiation and chemotherapeutic agents in two cell lines with different radiosensitivities and different p53 status.
abstract: BACKGROUND
  To investigate the differences between two rat yolk sac tumor cell lines with different radiosensitivities and p53 status in sensitivity to high-LET heavy-ion beam and in sensitizing effect of etoposide or cisplatin in combination with heavy-ion beam.
  
  
  METHODS
  NMT-1 (wild-type p53 cell) is a parent radiosensitive cell line and NMT-1R (mutant-type p53 cell) is a variant radioresistant cell line. Heavy ion (carbon ion) was accelerated to 290 MeV per nucleon by a heavy-ion medical accelerator in Chiba at National Institute of Radiological Sciences. The effects of carbon ion irradiation and carbon ion irradiation plus chemotherapeutic agents were assessed by clonogenic assay.
  
  
  RESULTS
  There was no significant difference between NMT-1 cells and NMT-1R cells in sensitivity to high-LET heavy-ion irradiation. The RBE of carbon beam was larger in mutant-type p53 cells than in wild-type p53 cells. Etoposide showed a supra-additive effect in combination with carbon beam irradiation in NMT-1R cells. Etoposide potentiation in NMT-1R cells was manifested by the decrease in the slope of the radiation dose-response curve. On the other hand, cisplatin had no enhancement of radiosensitivity in either cell lines.
  
  
  CONCLUSIONS
  Our findings suggested that high-LET radiotherapy is expected to be effective for patients carrying radioresistant tumors and mutated p53 tumor cells. Etoposide might be effective for radioresistant tumors in combination with heavy-ion beam irradiation.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. taketaka@med.gunma-u.ac.jp
authors.forename: Takeo
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukawa
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Hirayama
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Musha
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ando
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002244:Carbon; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005047:Etoposide / Q000494:pharmacology*; D016158:Genes, p53; D063193:Heavy Ion Radiotherapy; D018499:Linear Energy Transfer; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D011836:Radiation Tolerance; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D002244:Carbon