Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts.

Basil V. Worgul, Lubomir Smilenov, David J. Brenner, Anna Junk, Wei Zhou, Eric J. Hall

Research output: Contribution to journalArticle

82 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9836-9839
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number15
DOIs
StatePublished - Jul 23 2002

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts.'. Together they form a unique fingerprint.

  • Cite this