Lethal Sectoring, Genomic Instability, and Delayed Division Delay in HeLa S3 Cells Surviving Alpha- or X-irradiation

Abstract

Lethal sectoring (LS) is the process for survival in which lethal damage remaining in irradiated cells is eliminated as lethal sector (offspring without reproductive integrity). This process occurs through the postirradiation 1st to 4th divisions with the accompanying appearance of a clonogenic progenitor (clonogen) (clonogenic sectoring: CS). The features of LS or CS and genomic instability (GI) were explored by analyzing the pedigrees of HeLa cells surviving alpha- (0.45 Gy) or X-irradiation (3 Gy) (20% survival dose). Most (approximately 70%) of the lethal latent damage was eliminated from alpha-particle survivors through the 1st to 2nd divisions, but it persisted in X-ray survivors until the 2nd generation. Although the frequency of CS was similar to that of LS for alpha-irradiation, CS was higher than LS for X-irradiation. Nonlethal damage remaining in the clonogens led to an elevated incidence of delayed cell death in their progeny. The mean incidence was higher for alpha-particle (16.3%) than X-ray survivors (8.3%), indicating the greater potentiality for GI by alpha-particles. Evidence is available to suggest the intrinsic difference in the mechanisms of GI induction by these two radiations: the association of misrepaired clustered DNA damage (CD) with alpha-particles and unrepaired PLD with X-rays. A novel phenomenon, "delayed division delay (DDD)" was noticed, though occasionally (approximately 10% per cell), with the progeny during the postirradiation 1st-3rd generations. DDD was much longer in alpha- (mean: approximately 11 h) than X-irradiated cells (approximately 4 h). Supposedly DDD was triggered by delayed chromosome breakage. However, a significant shortening of cell-cycle time at the postirradiation 1st generation was recognized with X-ray survivors.