Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines

Abstract

Purpose: To investigate the cytotoxic effect of high linear-energy transfer (LET) carbon irradiation on glioblastoma cells lines in combination with temozolomide (TMZ).

Methods and materials: The cell lines U87-MG expressing wild-type p53 and LN229 expressing both mutant and wild-type p53 were irradiated with monoenergetic carbon ion beams (LET 172 keV/μm) or an extended Bragg peak (LET 103 keV/μm) after treatment with 10 μM or 20 μM TMZ. Cytotoxicity was measured by a clonogenic survival assay, and cell growth as well as cell cycle progression, were examined.

Results: The p53 mutant was more sensitive to X-ray irradiation than the p53 wild type cell line, which was also expressed in a shorter G2 block. High LET carbon ions show an increased biological effectiveness in both cell lines, which is consistent with the predictive calculations by the Local Effect Model (LEM) introduced by Scholz et al. The cell line LN229 was more sensitive to TMZ treatment than the U87MG cell line expressing wild-type p53 only. The combination of TMZ and irradiation showed an additive effect in both cell lines.

Conclusion: High LET carbon ion irradiation is significantly more effective for glioblastoma cell lines compared to photon irradiation. An additional treatment with TMZ may offer a great chance especially for several tumor types.

Keywords:

• Human glioma cells
• temozolomide
• carbon ion radiotherapy
• relative biological effectiveness (RBE)