title: Fas is involved in the p53-dependent apoptotic response to ionizing radiation in mouse testis.
abstract: Apoptosis induced in male germ cells following ionizing radiation is dependent on functional p53 (Trp53) being present. We sought to determine whether Fas (Tnfrsf6/CD95/APO-1), an apoptotic factor, is involved in this p53-dependent germ cell death. In p53 knock-out mice exposed to 5 Gy of x-radiation, germ cells were protected from cell death, as assessed by counting apoptotic seminiferous tubules 12 h following radiation. Similarly, spermatid head counts in p53 knock-out mice remained near normal 29 days after exposure to 0.5 Gy of radiation, whereas wild-type animals had a more than twofold reduction in spermatid head counts. Fas mRNA expression remained at pretreatment levels in p53 knock-out mice; however, Fas increased in a time-dependent manner in wild-type mice following exposure to 5 Gy of radiation, indicating that radiation-induced Fas expression is p53-dependent. The functional significance of Fas involvement was demonstrated when lpr(cg) mice, having a nonfunctional Fas receptor, were exposed to 5 Gy of radiation; the number of apoptotic seminiferous tubules 12 h following radiation was significantly reduced compared to that of wild-type mice. Additionally, lpr(cg) mice exposed to 0.5 Gy of radiation had increased spermatid head counts 29 days following radiation compared to wild-type mice. Interestingly, gld mice with a non-functional Fas ligand (Tnfsf6/FasL/CD95L) were as sensitive to radiation as wild-type animals, and levels of FasL mRNA were not affected by radiation treatment. These results indicate that apoptosis and up-regulation of Fas following radiation are both p53-dependent events. Although Fas is necessary, in part, for radiation-induced p53-dependent apoptosis, FasL is not.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, 171 Meeting Street, Providence, Rhode Island 02912, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Embree-Ku
authors.forename: Deborah
authors.initials: D
authors.lastname: Venturini
authors.forename: Kim
authors.initials: K
authors.lastname: Boekelheide
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D053222:Fas Ligand Protein; D016158:Genes, p53 / Q000502:physiology*; D005838:Genotype; D005854:Germ Cells / Q000502:physiology / Q000528:radiation effects; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013087:Spermatids / Q000528:radiation effects; D013737:Testis / Q000166:cytology* / Q000528:radiation effects*; D014965:X-Rays; D019014:fas Receptor / Q000502:physiology*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D004247:DNA