Chromosomal aberrations per charged particle per cell nucleus: Studies at the Radiological Research Accelerator Facility

Abstract

Chromosomal alterations are responsible for a significant proportion of cellular lethality and of genetic mutations, as well as being specifically associated with human cancers. For ionizing radiations the principal determinant of aberration likelihood is the linear energy transfer (LET). For radiation protection considerations one energy deposition event per cell nucleus is the ultimate low dose and such an approach bypasses traditional concepts of absorbed dose and relative biological effectiveness. Well characterized charged particles (protons, deuterons, 3He, 4He) generated at the RARAF Van de Graaff accelerator have been used to irradiate mammalian cells at LETs varying from 10 to 150 keV/μm. Measurements of the nuclear cross-sectional areas of mammalian cells at different stages of the cell cycle and known fluences of charged particles (per absorbed dose) at each LET enable relationships to be determined between charged particle incidence and both frequencies and types of chromosomal changes. Nuclear cross-sectional areas of cells tend to be log-normally distributed with overlapping distributions for the different stages of the cell cycle. There is a clear and profound effect of charged particle LET on cellular progression through the cell cycle and the induction of chromosomal change, two confounding endpoints. While there are variations in sensitivity to aberration induction (and cell cycle progression) for the different stages of the cell cycle, as LET per particle increases linearly, aberration frequency increases quadratically to an LET of about 100 kev/μm. Analysis of chromosomal changes as a function of LET has implications for the attribution of uniformity to alpha particles of different effective LETs following radon daughter breakdown.