Slow elimination of phosphorylated histone gamma-H2AX from DNA of terminally differentiated mouse heart cells in situ.
Phosphorylation of replacement histone H2AX occurs in megabase chromatin domains around double-strand DNA breaks (DSBs) and this modification (called gamma-H2AX) may serve as a useful marker of genome damage and repair in terminally differentiated cells. Here using immunohistochemistry we studied kinetics of gamma-H2AX formation and elimination in the X-irradiated mouse heart and renal epithelial tissues in situ. Unirradiated tissues have 3-5% gamma-H2AX-positive cells and in tissues fixed 1h after X-irradiation gamma-H2AX-positive nuclei are induced in a dose-dependent manner approaching 20-30% after 3 Gy of IR. Analysis of mouse tissues at different times after 3 Gy of IR showed that maximal induction of gamma-H2AX in heart is observed 20 min after IR and then is decreased slowly with about half remaining 23 h later. In renal epithelium maximum of the gamma-H2AX-positive cells is observed 40 min after IR and then decreases to control values in 23 h. This indicates that there are significant variations between non-proliferating mammalian tissues in the initial H2AX phosphorylation rate as well as in the rate of gamma-H2AX elimination after X-irradiation, which should be taken into account in the analysis of radiation responses.
Gavrilov
Boris
B
Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russian Federation.
Vezhenkova
Irina
I
Firsanov
Denis
D
Solovjeva
Liudmila
L
Svetlova
Maria
M
Mikhailov
Vyacheslav
V
Tomilin
Nikolai
N
D000818:Animals; D002454:Cell Differentiation; D004249:DNA Damage / Q000502:physiology*; D005260:Female; D006321:Heart / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D014916:Whole-Body Irradiation; D014965:X-Rays
D006657:Histones; C475961:gamma-H2AX protein, mouse