Direct and delayed X-ray-induced DNA damage in male mouse germ cells.
Sperm DNA integrity is essential for the accurate transmission of paternal genetic information. Various stages of spermatogenesis are characterized by large differences in radiosensitivity. Differentiating spermatogonia are susceptible to radiation-induced cell killing, but some of them can repair DNA damage and progress through differentiation. In this study, we applied the neutral comet assay, immunodetection of phosphorylated H2AX (γ-H2AX) and the Sperm Chromatin Structure Assay (SCSA) to detect DNA strand breaks in testicular cells and spermatozoa at different times following in vivo X-ray irradiation. Radiation produced DNA strand breaks in testicular cells that were repaired within the first few hours after exposure. Spermatozoa were resistant to the induction of DNA damage, but non-targeted DNA lesions were detected in spermatozoa derived from surviving irradiated spermatogonia. These lesions formed while round spermatids started to elongate within the testicular seminiferous tubules. The transcription of pro-apoptotic genes at this time was also enhanced, suggesting that an apoptotic-like process was involved in DNA break production. Our results suggest that proliferating spermatogonia retain a memory of the radiation insult that is recognized at a later developmental stage and activates a process leading to DNA fragmentation.
Laboratory of Toxicology, ENEA CR Casaccia, Rome, Italy. eugenia.cordelli@enea.it
Eugenia
E
Cordelli
Patrizia
P
Eleuteri
Maria Giuseppa
MG
Grollino
Barbara
B
Benassi
Giovanni
G
Blandino
Cecilia
C
Bartoleschi
Maria Chiara
MC
Pardini
Edoardo Vittorio
EV
Di Caprio
Marcello
M
Spanò
Francesca
F
Pacchierotti
Paola
P
Villani
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D009154:Mutation / Q000528:radiation effects*; D013091:Spermatogenesis / Q000528:radiation effects; D013094:Spermatozoa / Q000528:radiation effects*; D013737:Testis / Q000528:radiation effects; D014965:X-Rays / Q000009:adverse effects*