Short telomeres result in organismal hypersensitivity to ionizing radiation in mammals.
Here we show a correlation between telomere length and organismal sensitivity to ionizing radiation (IR) in mammals. In particular, fifth generation (G5) mouse telomerase RNA (mTR)(-/)- mice, with telomeres 40% shorter than in wild-type mice, are hypersensitive to cumulative doses of gamma rays. 60% of the irradiated G5 mTR(-/)- mice die of acute radiation toxicity in the gastrointestinal tract, lymphoid organs, and kidney. The affected G5 mTR(-/)- mice show higher chromosomal damage and greater apoptosis than similarly irradiated wild-type controls. Furthermore, we show that G5 mTR(-/)- mice show normal frequencies of sister chromatid exchange and normal V(D)J recombination, suggesting that short telomeres do not significantly affect the efficiency of DNA double strand break repair in mammals. The IR-sensitive phenotype of G5 mTR(-/)- mice suggests that telomere function is one of the determinants of radiation sensitivity of whole animals.
Goytisolo
F A
FA
Department of Immunology and Oncology, Centro Nacional de Biotecnología-CSIC, Campus Cantoblanco, E-28049 Madrid, Spain.
Samper
E
E
Martín-Caballero
J
J
Finnon
P
P
Herrera
E
E
Flores
J M
JM
Bouffler
S D
SD
Blasco
M A
MA
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000528:radiation effects; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D002478:Cells, Cultured; D004254:DNA Nucleotidyltransferases; D004260:DNA Repair; D005720:Gamma Rays; D007421:Intestine, Small / Q000473:pathology / Q000528:radiation effects; D007668:Kidney / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance / Q000235:genetics*; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange; D013154:Spleen / Q000166:cytology / Q000528:radiation effects; D013270:Stomach / Q000473:pathology / Q000528:radiation effects; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics / Q000502:physiology*; D045567:VDJ Recombinases
D017304:Annexin A5; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases; D019098:Telomerase