title: The relative biological effectiveness of densely ionizing heavy-ion radiation for inducing ocular cataracts in wild type versus mice heterozygous for the ATM gene.
abstract: The accelerated appearance of ocular cataracts at younger ages has been recorded in both astronauts and airline pilots, and is usually attributed to high-energy heavy ions in galactic cosmic ray radiation. We have previously shown that high-LET 1-GeV/nucleon (56)Fe ions are significantly more effective than X-rays in producing cataracts in mice. We have also shown that mice haploinsufficient for ATM develop cataracts earlier than wild-type animals, when exposed to either low-LET X-rays or high-LET (56)Fe ions. In this paper we derive quantitative estimates for the relative biological effectiveness (RBE) of high energy (56)Fe ions compared with X-rays, both for wild type and for mice haploinsufficient for ATM. There is a clear trend toward higher RBE's in haploinsufficient animals, both for low- and high-grade cataracts. Haploinsufficiency for ATM results in an enhanced sensitivity to X-rays compared with the wild type, and this enhancement appears even larger after exposure to high-LET heavy ions.
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA. ejh1@columbia.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hall
authors.forename: Basil V
authors.initials: BV
authors.lastname: Worgul
authors.forename: Lubomir
authors.initials: L
authors.lastname: Smilenov
authors.forename: Carl D
authors.initials: CD
authors.lastname: Elliston
authors.forename: David J
authors.initials: DJ
authors.lastname: Brenner
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002386:Cataract / Q000209:etiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D020450:Heavy Ions; D006579:Heterozygote; D007501:Iron; D018499:Linear Energy Transfer; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000235:genetics*; D012062:Relative Biological Effectiveness; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014965:X-Rays
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D007501:Iron; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases