Induction of DNA double-strand breaks by 157Gd neutron capture.
The rationale of boron (10B) neutron capture therapy (BNCT) is based on the high thermal neutron capture cross section of 10B and the limited maximum range (about one cell diameter) of the high LET fission products of the boron neutron capture (NC) reaction. The resulting radiochemical damage is confined to the cell containing the BNC reaction. Although other nuclides have higher thermal neutron capture cross sections than 10B, NC by such nuclides results in the emission of highly penetrating gamma rays. However, gadolinium-157 (157Gd) n-gamma reaction is also accompanied by some internal conversion and, by implication, Auger electron emission. Irradiation of Gd3+-DNA complexes with thermal neutrons results in the induction of DNA double-strand (ds) breaks, but the effect is largely abrogated in the presence of EDTA. Thus, by analogy with the effects of decay of Auger electron-emitting isotopes such as 125I, the Gd NC event must take place in the close proximity of DNA in order to induce a DNA ds break. It is proposed that 157Gd-DNA ligands therefore have potential in NCT. The thermal neutron capture cross section of 157Gd, a nonradioactive isotope, is more than 50 times that of 10B.
Martin
R F
RF
Molecular Science Group, Peter MacCallum Cancer Institute, Melbourne, New South Wales, Australia.
D'Cunha
G
G
Pardee
M
M
Allen
B J
BJ
D004247:DNA / Q000528:radiation effects* / Q000648:ultrastructure; D004249:DNA Damage; D005682:Gadolinium / Q000378:metabolism / Q000494:pharmacology*; D007554:Isotopes; D009502:Neutrons; D010957:Plasmids; D011878:Radiotherapy / Q000379:methods
D007554:Isotopes; D004247:DNA; D005682:Gadolinium