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.

MATERIALS AND 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.

CONCLUSION:

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: Takeo Takahashi, Takeshi Fukawa, Ryoichi Hirayama, Yukari Yoshida, Atsushi Musha, Yoshiya Furusawa, Koichi Ando, Takashi Nakano
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 6 Pg. 1961-7 (Jun 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 20651340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Etoposide
• Carbon

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Carbon
• Cell Line, Tumor
• Combined Modality Therapy
• Dose-Response Relationship, Radiation
• Etoposide (pharmacology)
• Genes, p53
• Heavy Ion Radiotherapy
• Linear Energy Transfer
• Neoplasms (genetics, therapy)
• Radiation Tolerance
• Rats