Effects of 1 GeV/nucleon ⁵⁶Fe particles on longevity, carcinogenesis and neuromotor ability in Atm-deficient mice.
As therapeutic uses of high-LET radiation become more prevalent and human space exploration continues to be a focus of NASA, it is important to understand the biological effects of high-LET radiation and the role of genetics in sensitivity to high-LET radiation. To study genetic susceptibility to radiation, we used mice deficient in Atm activity (AtmΔSRI). ATM is important in DNA repair, apoptosis and cell cycle regulation. Although homozygous mutations in ATM are rare, the prevalence of ATM heterozygosity is estimated to be 1% and results in an increased cancer risk. We found that the effects of 1 Gy 1 GeV/nucleon ⁵⁶Fe particles on life span and tumorigenesis are genotype- and sex-specific. Significant effects of 1 Gy 1 GeV/nucleon ⁵⁶Fe particles on incidence of non-cancer end points were seen; however, 2 Gy 1 GeV/nucleon ⁵⁶Fe particles significantly affected neuromotor ability. Our results represent an extensive investigation into the late effects of high-LET radiation exposure in a sex- and genotype-dependent manner and provide a baseline for understanding the long-term risks of high-LET radiation.
Department of Pathology and Laboratory Medicine, University of California-Los Angeles, 650 Charles E. Young Dr. South, Los Angeles, CA 90095, USA.
Mitsuko L
ML
Yamamoto
Kurt
K
Hafer
Ramune
R
Reliene
Sheila
S
Fleming
Owen
O
Kelly
Katrin
K
Hacke
Robert H
RH
Schiestl
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D005838:Genotype; D005978:Glutathione / Q000378:metabolism; D020450:Heavy Ions; D007501:Iron; D018499:Linear Energy Transfer; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012737:Sex Factors; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D007501:Iron; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D005978:Glutathione