Ahmed EA, Agay D, Schrock G, Drouet M, Meineke V, Scherthan H, et al.
PloS one. Date of publication 2012 Jan 1;volume 7(6):e39521.
1. PLoS One. 2012;7(6):e39521. doi: 10.1371/journal.pone.0039521. Epub 2012 Jun 27.
Persistent DNA damage after high dose in vivo gamma exposure of minipig skin.
Ahmed EA(1), Agay D, Schrock G, Drouet M, Meineke V, Scherthan H.
Author information:
(1)Institut für Radiobiologie der Bundeswehr in Verbindung mit der Universität
Ulm, München, Germany.
BACKGROUND: Exposure to high doses of ionizing radiation (IR) can lead to
localized radiation injury of the skin and exposed cells suffer dsDNA breaks that
may elicit cell death or stochastic changes. Little is known about the DNA damage
response after high-dose exposure of the skin. Here, we investigate the cellular
and DNA damage response in acutely irradiated minipig skin.
METHODS AND FINDINGS: IR-induced DNA damage, repair and cellular survival were
studied in 15 cm(2) of minipig skin exposed in vivo to ~50 Co-60 γ rays. Skin
biopsies of control and 4 h up to 96 days post exposure were investigated for
radiation-induced foci (RIF) formation using γ-H2AX, 53BP1, and active ATM-p
immunofluorescence. High-dose IR induced massive γ-H2AX phosphorylation and high
53BP1 RIF numbers 4 h, 20 h after IR. As time progressed RIF numbers dropped to a
low of <1% of keratinocytes at 28-70 days. The latter contained large RIFs that
included ATM-p, indicating the accumulation of complex DNA damage. At 96 days
most of the cells with RIFs had disappeared. The frequency of
active-caspase-3-positive apoptotic cells was 17-fold increased 3 days after IR
and remained >3-fold elevated at all subsequent time points. Replicating basal
cells (Ki67+) were reduced 3 days post IR followed by increased proliferation and
recovery of epidermal cellularity after 28 days.
CONCLUSIONS: Acute high dose irradiation of minipig epidermis impaired stem cell
replication and induced elevated apoptosis from 3 days onward. DNA repair cleared
the high numbers of DBSs in skin cells, while RIFs that persisted in <1% cells
marked complex and potentially lethal DNA damage up to several weeks after
exposure. An elevated frequency of keratinocytes with persistent RIFs may thus
serve as indicator of previous acute radiation exposure, which may be useful in
the follow up of nuclear or radiological accident scenarios.
DOI: 10.1371/journal.pone.0039521
PMCID: PMC3384646
PMID: 22761813 [Indexed for MEDLINE]
