In vitro interaction of high-LET heavy-ion irradiation and chemotherapeutic agents in two cell lines with different radiosensitivities and different p53 status.
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.
Takahashi
Takeo
T
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
Fukawa
Takeshi
T
Hirayama
Ryoichi
R
Yoshida
Yukari
Y
Musha
Atsushi
A
Furusawa
Yoshiya
Y
Ando
Koichi
K
Nakano
Takashi
T
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
D000970:Antineoplastic Agents; D005047:Etoposide; D002244:Carbon