Abstract
A Novel Phenomenon "Delayed Division Delay": Evidence for Delayed DNA Double-Strand Break and Rejoining in the Clonogenic Progeny of HeLa Cells Surviving Alpha or X Irradiation
Hiroshi SASAKI (retired from The Dept. Exp. Radiol., Kyushu Univ.)
Lethal sectoring is the process for survival by which lethal damage remaining in irradiated cells is eliminated as offspring without reproductive integrity, and occurs through the postirradiation 1st-4th divisions with the accompanying appearance of a clonogenic progenitor harboring no lethal damage. However, nonlethal damage remaining in the clonogenic progenitors led to an elevated incidence of delayed cell death in their progeny. From an analysis of the pedigrees of cells surviving alpha (0.45 Gy) or X irradiation (3 Gy) (20% survival dose), it became clear that the mean incidence was higher for alpha-particle (16.3%) than X-ray survivors (8.3%), indicating the greater potentiality for genomic instability by alpha particles. Evidence is available to suggest the association of misrepaired clustered DNA damage with alpha particles.
A novel phenomenon "delayed division delay (DDD)" was noticed, though occasionally (ca.10% per cell; ca.30% per pedigree), with the clonogenic progeny during the postirradiation 1st-3rd generations. DDD was much longer in alpha- (mean: ca.11 h) than X-irradiated cells (ca.4 h), and might be triggered by delayed DNA double-strand breaks at the fragile break-misrejoining sites. This demonstrates the usefulness of DDD as a new endpoint of radiation-induced genomic instability.
