Induction of chromosome aberrations in unirradiated chromatin after partial irradiation of a cell nucleus.
OBJECTIVE
It is generally accepted that chromosome exchanges in irradiated cells are formed through interactions between separate DNA double-strand breaks (DSB). Here we tested whether non-irradiated DNA participates in the formation of chromosome aberrations when complex DNA DSB are induced elsewhere in the nucleus.


METHODS
Synchronized Chinese hamster cells containing an X chromosome with a late replicating q arm (X(q) domain) were labelled with 125I-iododeoxyuridine (125IdUrd) in a period of S-phase when the vast majority of the X(q) domain was not replicating. DNA damage from 125I decay was accumulated at the G1/S border while the cells were stored in liquid nitrogen. Decay of 125I induced DSB in the immediate vicinity of the 125I atom. Chromosome aberrations involving what is essentially the 125I-free X domain were scored at the first mitosis after cell thawing. As a positive control, cells were treated with 125IdUrd at a later period in S-phase when the X(q) domain replicates, yielding a labelled X(q) domain.


RESULTS
The 125I-free X(q) domain exhibited chromosome aberrations (exchanges and fragments). The frequency of these aberrations was linearly dependent on the number of 125I decays elsewhere in the cell nucleus. The efficiency of formation of chromosome aberrations by the 125I-free X(q) domain was approximately half of that observed in the 125I-labelled X(q) domain.


CONCLUSIONS
The involvement of the 125I-free X(q) domain in chromosome aberrations suggests that DNA not damaged by the decay of incorporated 125I can interact with damaged DNA, indicating the existence of an alternative pathway for the formation of chromosome aberrations.
Ludwików
G
G
Center for Microscopical Research, Department of Cell Biology, University of Amsterdam, Amsterdam, The Netherlands.
Xiao
Yun
Y
Hoebe
R A
RA
Franken
N A P
NA
Darroudi
F
F
Stap
J
J
Van Oven
C H
CH
Van Noorden
C J F
CJ
Aten
J A
JA
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects*; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D002869:Chromosome Aberrations / Q000528:radiation effects*; D006224:Cricetinae; D004249:DNA Damage; D007065:Idoxuridine / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D007457:Iodine Radioisotopes; D008957:Models, Genetic; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects
D002843:Chromatin; D007457:Iodine Radioisotopes; D007065:Idoxuridine