Radiation Cataract and Mitosis

Worgul, Basil V.; Rothstein, H.

doi:10.1159/000264731

Cited by 59 publications

(19 citation statements)

References 7 publications

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“…Radiation-induced cataracts have been studied in cancer patients (16), patients under- (20,21). Cataract severity and time of onset are directly related to the number of genomically damaged cells attempting differentiation (fibergenesis) (22,23).…”

Section: Discussionmentioning

confidence: 99%

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

Worgul

Smilenov

Brenner

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

106

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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.

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Section: Discussionmentioning

confidence: 99%

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

Worgul

Smilenov

Brenner

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

106

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“…W o r g u l and R othstkin [44] also found that depressing the mitotic activity of frogs by keeping them at very low temperatures reduced the in cidence and severity of cataracts produced by ionizing radiation. They con cluded that mitosis 'transduced' epithelial cell damage into cataractous changes and that inhibition of mitosis prevented this transduction.…”

Section: Dna Repair In the Lensmentioning

confidence: 95%

The Role of DNA damage, its Repair and its Misrepair in the Etiology of Cataract: a Review

Jose

1978

Ophthalmic Res

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A hypothesis is presented regarding the importance of desoxyribonuclei acid (DNA) repair for maintenance of lens clarity. It is proposed that unrepaired or incorrectly repaired damage to lens epithelial cell DNA may result in decreased lens transparency either by altering normal metabolism in the epithelium or subsequently by affecting lens cell differentiation and protein synthesis in the lens cortex.

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“…While other environmental insults might also result in formation of posterior subcapsular cataracts, radiation-induced cataracts are generally associated with this form of lens opacification (32,33). Its development is directly related to radiation dose and also depends on the rate at which damaged lens epithelial cells divide, aberrantly differentiate and migrate to the posterior pole (34). Although the precise inducing mechanism is not known, it is generally accepted that genomic damage results in altered cell division, transcription and/or abnormal lens fiber cell differentiation that leads to cataract development (35,36).…”

Section: Introductionmentioning

confidence: 99%

Mrad9 and Atm Haploinsufficiency Enhance Spontaneous and X-Ray-Induced Cataractogenesis in Mice

et al. 2007

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Rad9 and Atm regulate multiple cellular responses to DNA damage, including cell cycle checkpoints, DNA repair and apoptosis. However, the impact of dual heterozygosity for Atm and Rad9 is unknown. Using 50 cGy of X rays as an environmental insult and cataractogenesis as an end point, this study examined the effect of heterozygosity for one or both genes in mice. Posterior subcapsular cataracts, characteristic of radiation exposure, developed earlier in X-irradiated double heterozygotes than in single heterozygotes, which were more prone to cataractogenesis than wild-type controls. Cataract onset time and progression in single or double heterozygotes were accelerated even in unirradiated eyes. These findings indicate that the cataractogenic effect of combined heterozygosity is greater than for each gene alone and are the first to demonstrate the impact of multiple haploinsufficiency on radiation effects in an intact mammal. These observations may help explain observed interindividual differential radiosensitivity in human populations and have important implications for those undergoing radiotherapy or exposed to elevated levels of cosmic radiation, such as the astronaut corps. These findings demonstrate that Mrad9 and Atm are important determinants of lens opacification and, given the roles of Atm and Rad9 in maintaining genomic stability, are consistent with a genotoxic basis for radiation cataractogenesis. ᭧ 2007 by Radiation Research Society

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Radiation Cataract and Mitosis

Cited by 59 publications

References 7 publications

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

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

The Role of DNA damage, its Repair and its Misrepair in the Etiology of Cataract: a Review

Mrad9 and Atm Haploinsufficiency Enhance Spontaneous and X-Ray-Induced Cataractogenesis in Mice

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