Dose-response and relative biological effectiveness of fast neutrons: induction of apoptosis and inhibition of neurogenesis in the hippocampus of adult mice.

PURPOSE

Our study compared the effects of high linear energy transfer (LET) fast neutrons on the induction of apoptosis and reduction of neurogenesis in the hippocampus of adult ICR mice with those of low-LET (60)Co gamma-rays, to evaluate the relative biological effectiveness (RBE) of fast neutrons in the adult hippocampal dentate gyrus (DG).

MATERIALS AND METHODS

The mice were exposed to 35 MeV fast neutrons or (60)Co gamma-rays. We evaluated acutely the incidence of apoptosis and expression of Ki-67 (a protein marker for cell proliferation originally defined by the monoclonal antibody Kiel-67) and doublecortin (DCX: an immature progenitor neuron marker) in the hippocampus after a single whole-body irradiation.

RESULTS

The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL)-positive apoptotic nuclei in the DG increased and both Ki-67- and DCX-positive cells declined in a dose-dependent pattern, with fast neutrons or gamma-rays. In the hippocampus, which showed an apoptosis frequency between 2 and 8 per DG, the RBE of fast neutrons was approximately 1.9. Additionally, the inhibitory effects of fast neutrons on the expression frequencies of Ki-67 (4-8) and DCX (8-32) were approximately 3.2 and 2.5 times, respectively, the effects of gamma-rays at the same dose.

CONCLUSIONS

Increased apoptotic cell death and decreased neurogenesis in the hippocampal DG were seen in a dose-dependent pattern after exposure to fast neutrons and gamma-rays. In addition, the different rate of hippocampal neurogenesis between different radiation qualities may be an index of RBE.