In Vitro Split-Dose Recovery of Glioblastoma Multiforme

Abstract

Glioblastoma multiforme is among the most clinically resistant tumors to radiation. This resistance may be due to several different factors, such as a low intrinsic radiation sensitivity, a high recovery capacity, an increased number of clonogens, and a high hypoxic fraction. Previously, we have demonstrated a very wide range of intrinsic radiation sensitivities of cells of glioblastoma multiforme cell lines in vitro after single-dose irradiation. That is, the cells of some glioblastoma multiforme cell lines were quite sensitive, while for others the sensitivity of glioblastoma multiforme was among the lower range of sensitivities reported in the literature. This finding indicates that inherent cellular radiation sensitivity is not the sole determinant of the in vivo response of glioblastoma multiforme tumors. In this report, we evaluate the role of split-dose recovery determined in vitro in relation to the poor clinical outcome of glioblastoma multiforme. Cells of seven early-passage glioblastoma multiforme cell lines and six cell lines derived from tumors of a type frequently treated successfully (two squamous cell carcinomas of head and neck, three breast cancers, and one low-grade astrocytoma cell line) were studied. The in vitro split-dose recovery has been measured using colony formation as an end point. The cells were maintained at 37 degrees C for a period of 6 h between the doses of radiation. Results are presented in terms of a recovery ratio: the ratio of the mean inactivation dose of split-dose radiation to that of single-dose radiation. The data show significantly higher recovery ratios for glioblastoma multiforme than for the other types of histology; however, glioblastoma multiforme showed a wide range of recovery ratios, varying from 1.12 to 2.02. This indicates that cells of some glioblastoma multiforme cell lines exhibit minimal split-dose recovery. No correlation was found between the recovery ratio and the intrinsic radiation sensitivity of the cell lines studied. From these data, we conclude that the recovery capacity may not be the major determinant of the clinical radiation resistance of some glioblastoma multiforme.