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Record 10 of 608
Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts
External Online Source: doi:10.1073/pnas.162349699
Author and Affiliation:
Worgul, Basil V.(Columbia University, College of Physicians and Surgeons, Eye Radiation and Environmental Research Laboratory and Center for Radiological Research, New York, NY 10032, United States)
Smilenov, Lubomir
Brenner, David J.
Junk, Anna
Zhou, Wei
Hall, Eric J.
Abstract: It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM(+/-)) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM(+/-) cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.
Publication Date: Jul 23, 2002
Document ID:
20040088227
(Acquired Sep 07, 2004)
Subject Category: AEROSPACE MEDICINE
Document Type: Journal Article
Publication Information: Proceedings of the National Academy of Sciences of the United States of America (ISSN 0027-8424); Volume 99; 15; 9836-9
Publisher Information: United States
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: CATARACTS; GENETICS; MICE; RADIATION INJURIES; RADIATION TOLERANCE; SENSITIVITY; ATAXIA; DISEASES; KNOCKOUT MICE; RADIATION EFFECTS; TIME DEPENDENCE
Other Descriptors: CATARACT/GENETICS; PROTEIN-SERINE-THREONINE KINASES/DEFICIENCY/GENETICS/PHYSIOLOGY; RADIATION INJURIES/GENETICS; RADIATION TOLERANCE/GENETICS; ANIMALS; ATAXIA TELANGIECTASIA/GENETICS; COMPARATIVE STUDY; DISEASE MODELS, ANIMAL; HOMOZYGOTE; MICE; MICE, KNOCKOUT; REFERENCE VALUES; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, NON-P.H.S; TIME FACTORS; NASA DISCIPLINE RADIATION HEALTH; NON-NASA CENTER
Availability Source: Other Sources
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