Chromosome Aberrations Induced in Human Lymphocytes by 3.45 MeV Alpha Particles Analyzed by Premature Chromosome Condensation

Abstract

Premature chromosome condensation (PCC) experiments using human lymphocytes with centromere staining have shown that after exposure to 3.45 MeV alpha-particle radiation, the full number of dicentric chromosomes appears when the cell fusion protocol is applied immediately after irradiation. In this case, the time available for repair and misrepair of DNA damage is only about 30 min. The number of dicentrics does not change with a further increase in the time available for chromatin rearrangement. This fast response confirms the expectation based on our previous experiments using PCC with 150 kV X rays in which the alpha component of the yield of dicentrics was found to appear when the cell fusion protocol was applied immediately after irradiation, whereas the beta component was delayed by several hours. The time constant for rejoining of the excess acentric chromosome fragments is found to be donor-specific and not to differ for alpha particles and X rays, but alpha-particle radiation leaves a larger fraction of the excess acentric fragments unrejoined. The RBEs of the 3.45 MeV alpha-particle radiation compared to 150 kV X rays, evaluated for the alpha component for the yield of dicentrics and for the yield of unrepaired acentric fragments, have almost equal values of about 4. This is consistent with data in the literature on chromosome aberrations observed in metaphase that show the equality of the RBE values for production of dicentrics and acentric fragments. Our experimental results concerning the fast kinetics of the alpha component of the yield of exchange-type chromosome aberrations are not consistent with Lea's pairwise lesion interaction model, and they support the proposed alternative mechanism of lesion-nonlesion interaction between chromatin regions carrying clustered DNA damage and intact chromatin regions.

Induction of reproductive cell death and chromosome aberrations in radioresistant tumour cells by carbon ions

“…The overall frequencies of lethal dicentrics in cells irradiated with a-particles (Durante et al 1992, Durante et al 1995, Schmid et al 1996, Moquet et al 2001 or ions , Ohara et al 1998, Greinert et al 1999, Durante et al 2000, 2002 were increased in a corresponding manner, thus confirming the correlation between clonogenic cell death and induction of dicentric chromosomes.…”

Healthy Tissue Damage Following Cancer Ion Therapy: A Radiobiological Database Predicting Lymphocyte Chromosome Aberrations Based on the BIANCA Biophysical Model

“…Data on lymphocyte dicentrics by He-ions were found in [ 24 ] (for 22.0 keV/μm 3 He ions), [ 25 ] (24.0 keV/μm 3 He ions and 140.0 keV/μm alpha particles), [ 26 ] (31.4 keV/μm 4 He ions), [ 27 ] (113.0 keV/μm alpha particles), [ 28 ] (150.0 keV/μm alpha particles), and [ 29 ] (155.0 keV/μm alpha particles). Figure 2 reports simulation outcomes and experimental data at 22.0, 31.4, 113.0 and 155.0 keV/μm.…”

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

“…For peripheral blood lymphocytes, the high micronuclei yield induced by neutron or ␣-particle irradiation has been attributed to a high proportion of non-reparable damage. 2,29,30 Differences in MN yield can be attributed to differences in DNA repair capacity. Although the rate of DNA repair has been shown to be similar after high and low LET irradiation, neutrons induce more dsb than photons and therefore produce high levels of residual unrejoined strand-breaks.…”