Micronucleus Response of Human Glioblastoma and Neuroblastoma Cells Toward Low-LET Photon and High-LET p(66)/Be Neutron Irradiation

Abstract

The identification of photon resistant tumors that are sensitive to neutrons is still an unresolved problem, and no radiobiological criteria have been developed that could help the selection of patients for neutron therapy. The micronucleus (MN) assay has been evaluated for this purpose in a panel of human glioblastoma and neuroblastoma cell lines spanning a wide range of photon sensitivities defined by mean inactivation doses ([Latin capital letter D with macron above][gamma]) of 1.25-3.21 Gy. We show that the relative biologic effectiveness (RBE) of the p(66)/Be neutrons is significantly correlated with inherent photon sensitivity (r = 0.89, p < 0.01), indicating that the panel of cell lines used is suitable to study the differential biologic response to neutrons and photons. We find that p(66)/Be neutrons are 1.43 to 5.29 times more effective per unit dose in inducing micronuclei than 60Co [gamma]-rays. Surprisingly, cells that are inherently photon resistant tend to show a higher yield of micronuclei following exposure to either photons or neutrons, but no significant correlation could be demonstrated. However, RBE values based on micronucleus yield were found to strongly correlate with RBE values derived from cell survival data (r = 0.91, p < 0.01). It is concluded that although micronucleus yield does not reflect intrinsic sensitivity to either photons or neutrons, the strong correlation between RBE calculated from micronucleus formation and RBE derived from cell survival demonstrates that the micronucleus endpoint has a potential for detecting photon resistant cells that show increased sensitivity to neutrons.

Changes in G1-phase populations in human glioblastoma and neuroblastoma cell lines influence p(66)/Be neutron-induced micronucleus yield

“…It has previously been shown that low energy first generation neutrons (mean energy of 6 MeV) discriminate between photon resistant and photon sensitive cells and that a significant increase of neutron RBE with photon resistance can be demonstrated . Using the same neutron beam, we have shown in a more recent study that RBE values obtained from MN data correlates significantly with RBE values derived from cell survival data, and that the MN assay shows potential as a useful tool for identifying photon-resistant tumours that may show neutron sensitivity (Akudugu et al, 2003). However, not all photon-resistant cell lines yielded expected RBE values from MN data.…”

“…The cell survival and micronucleus formation data used in the present discussion were adapted from a preceding study (Akudugu et al, 2003) and are summarised in Table 1. Cellular radiosensitivity was based on mean inactivation dose and cytokinesis-block micronucleus yield was defined as the slope of the micronucleus frequency (MNF)-dose response curves.…”