title: Mice heterozygous for the ATM gene are more sensitive to both X-ray and heavy ion exposure than are wildtypes.
abstract: Previous studies have shown that the eyes of ATM heterozygous mice exposed to low-LET radiation (X-rays) are significantly more susceptible to the development of cataracts than are those of wildtype mice. The findings, as well as others, run counter to the assumption underpinning current radiation safety guidelines, that individuals are all equally sensitive to the biological effects of radiation. A question, highly relevant to human space activities is whether or not, in similar fashion there may exist a genetic predisposition to high-LET radiation damage. Mice haplodeficient for the ATM gene and wildtypes were exposed to 325 mGy of 1 GeV/amu 56Fe ions at the AGS facility of Brookhaven National Laboratory. The fluence was equivalent to 1 ion per lens epithelial cell nuclear area. Controls consisted of irradiated wildtype as well as unirradiated wildtype and heterozygous mice. Prevalence analyses for stage 0.5-3.0 cataracts indicated that not only cataract onset but also progression were accelerated in the mice haplo-deficient for the ATM gene. The data show that heterozygosity for the ATM gene predisposes the eye to the cataractogenic influence of heavy ions and suggest that ATM heterozygotes in the human population may also be radiosensitive. This may have to be considered in the selection of individuals who will be exposed to both HZE particles and low-LET radiation as they may be predisposed to increased late normal tissue damage.
authors.affiliation: Eye Radiation and Environmental Research Laboratory, Columbia University, New York, NY 10032, USA. bvwl@columbia.edu
authors.forename: B V
authors.initials: BV
authors.lastname: Worgul
authors.forename: L
authors.initials: L
authors.lastname: Smilenov
authors.forename: D J
authors.initials: DJ
authors.lastname: Brenner
authors.forename: M
authors.initials: M
authors.lastname: Vazquez
authors.forename: E J
authors.initials: EJ
authors.lastname: Hall
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D002386:Cataract / Q000235:genetics*; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020450:Heavy Ions; D006720:Homozygote; D007501:Iron; D007908:Lens, Crystalline / Q000528:radiation effects; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D012062:Relative Biological Effectiveness; D017356:Synchrotrons; D025521:Tumor Suppressor Proteins; D014965:X-Rays
chemical_list: 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