F. Ianzini et Ma. Mackey, DELAYED DNA-DAMAGE ASSOCIATED WITH MITOTIC CATASTROPHE FOLLOWING X-IRRADIATION OF HELA S3 CELLS, Mutagenesis, 13(4), 1998, pp. 337-344
Partial loss of the radiation G2/M, checkpoint is thought to be an ear
ly event in cell immortalization, One of the attributes of immortalize
d cell lines is an increase in susceptibility to induction of genomic
instability by clastogenic agents. Recently we have shown that in irra
diated HeLa cells cell cycle delays in late S and G2 lead to overaccum
ulation of cyclin B1 and that enhanced intracellular levels of this po
sitive regulator of the cell cycle is correlated with cyclin-dependent
kinase activation, spontaneous premature chromosome condensation and
subsequent mitotic catastrophe occurring following irradiation. Previo
us studies have shown that spontaneous premature chromosome condensati
on anti mitotic catastrophe are independent of apoptosis, This report
shows that 40 h following X-irradiation of HeLa S3 cells, and subseque
nt to mitotic catastrophe, DNA strand breaks appear which are chemical
ly distinct from those initially produced by ionizing radiation, This
delayed damage is recognized by terminal transferase and thus involves
generation of free 3'-OH ends. Pulse field gel electrophoresis analys
is of DNA size distributions shows that DNA fragments of similar to 40
kbp and smaller are produced. As !strand breaks produced as a direct
result of irradiation are generally repaired within a few hours after
exposure to X-rays at the doses used, these results describe a novel m
echanism for generation of DNA damage occurring a day or more followin
g irradiation. These results may be pertinent to the understanding of
mechanisms underlying the delayed lethal effects of irradiation and ma
y provide an initiating mechanism for radiation-induced genomic instab
ility.