The relative biological effectiveness of densely ionizing heavy-ion radiation for inducing ocular cataracts in wild type versus mice heterozygous for the ATM gene.
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.
Hall
Eric J
EJ
Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA. ejh1@columbia.edu
Worgul
Basil V
BV
Smilenov
Lubomir
L
Elliston
Carl D
CD
Brenner
David J
DJ
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
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