THE DOSE-DEPENDENT FRAGMENTATION OF CHROMATIN IN HUMAN FIBROBLASTS BY 3.5-MEV ALPHA-PARTICLES FROM PU-238 - EXPERIMENTAL AND THEORETICAL CONSIDERATIONS PERTAINING TO SINGLE-TRACK EFFECTS

The technique of premature chromosome condensation (PCC) was used to examine the dose-response relationship for the production of interphase (G0) chromosome fragments in noncycling normal human fibroblasts following exposure to 238Pu α particles, with special emphasis on the low-dose region. The dose response was convincingly linear from 0.2 to 3.0 Gy. Analysis of further data collected over a dose range of 1.1 to 22.4 cGy provided no evidence of deviation from linearity in this low-dose region. The fact that this lower dose range extends into the region where single-particle effects are dominant suggests that a linear extrapolation of this response from higher to lower doses is valid. Ratios of coefficients for the induction of fragments produced by 238Pu α particles versus 60Co γ rays gave an RBE of 2.34 ± 0.09. Distributions of fragments among 60Co γ-irradiated cells were consistent with a Poisson expectation of random damage. In contrast, overdispersion appeared to be a general feature of 238Pu α-particle-induced fragmentation, a phenomenon explainable under the assumption that single-particle traversals are capable of producing multiple PCC fragments. Data obtained were used to estimate practical and theoretical lower-dose limits of detection of initial chromatin breaks provided by current PCC methodology.