PARP inhibitor 3-aminobenzamide does not increase the yields of chromosomal aberrant cells induced by boron neutron capture reaction in V79 Chinese hamster cells

Full text: Mechanistic knowledge on DNA and cell damage induced by alpha-particles remains limited. It is well known that high-LET radiation induces both DNA single (ssb) and double strand breaks (dsb), being the latter frequently associated with cell death. The repair of these DNA lesions and specially dsb are thus fundamental for the understanding of high-LET radiation effects. Poly (ADP-ribose) polymerase is a nuclear enzyme, which detects and signals DNA strand breaks (ssb and dsb). The important role of this enzyme in the maintenance of DNA integrity has been extensively studied for genotoxic chemicals and low-LET ionizing radiation. Nevertheless, sparse information concerning the role of PARP in high-LET radiation effects is available. The purpose of this work is to examine whether the PARP inhibitor 3-aminobenzamide (3-AB) enhances the yields of chromosomal aberrations induced by the boron neutron capture (BNC) reaction in V79 Chinese hamster cells. Wild-type V79 cells were pre-incubated for 48 hours with different concentrations (0.48-2.4 mM) of the boron delivery agent 4-borono-L-phenylalanine (BPA) and then irradiated for different periods of time with thermal neutrons. In the 3-AB treated cultures, four hours before the irradiation the cells were incubated with different concentrations of this inhibitor (1.5-10 mM) which remained in culture until colchicine was added. The chromosomal aberrations assay was performed according to standard protocol. A clear dose-response in the frequencies of chromosomal aberrant cells excluding gaps (%CAEG) induced by the BNC reaction was observed for both BPA concentration and thermal neutron fluence. There was no evidence of an increase in the % CAEG induced after incubation with 3-AB. Some cytoxicity was observed (mitotic index) after 3-AB incubation in BPA irradiated cells. In conclusion, the clastogenic potential of the alpha-particles generated through the BNC reaction was not affected by using a classic PARP inhibition approach. (author)