Combs Stephanie E, Bohl Jessica, Elsasser Thilo, Weber Klaus-Josef, Schulz-Ertner Daniela, Debus Jurgen, Weyrather Wilma K
Department of Radiation Oncology, University of Heidelberg.
Int J Radiat Biol. 2009 Feb;85(2):126-37. doi: 10.1080/09553000802641151.
To investigate the cytotoxic effect of high linear-energy transfer (LET) carbon irradiation on glioblastoma cells lines in combination with temozolomide (TMZ).
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/microm) or an extended Bragg peak (LET 103 keV/microm) after treatment with 10 microM or 20 microM TMZ. Cytotoxicity was measured by a clonogenic survival assay, and cell growth as well as cell cycle progression, were examined.
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.
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.
研究高传能线密度（LET）碳离子辐照联合替莫唑胺（TMZ）对胶质母细胞瘤细胞系的细胞毒性作用。
用10微摩尔或20微摩尔TMZ处理后，对表达野生型p53的U87-MG细胞系和同时表达突变型及野生型p53的LN229细胞系，用单能碳离子束（LET 172千电子伏/微米）或扩展布拉格峰（LET 103千电子伏/微米）进行辐照。通过克隆形成存活试验测量细胞毒性，并检测细胞生长以及细胞周期进程。
p53突变体比p53野生型细胞系对X射线辐照更敏感，这也表现为较短的G2期阻滞。高LET碳离子在两种细胞系中均显示出更高的生物学效应，这与Scholz等人提出的局部效应模型（LEM）的预测计算结果一致。LN229细胞系比仅表达野生型p53的U87MG细胞系对TMZ治疗更敏感。TMZ与辐照联合在两种细胞系中均显示出相加效应。
与光子辐照相比，高LET碳离子辐照对胶质母细胞瘤细胞系的效果显著更好。尤其是对于几种肿瘤类型，额外使用TMZ治疗可能提供很大机会。
