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

Jose, Jule Griebrok

doi:10.1159/000264935

Cited by 42 publications

(16 citation statements)

References 33 publications

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“…I have discussed elsewhere that there may be a causal relationship between DNA damage and cataracts (3). Because of this relationship and the reported connection between chlorpromazine and lens opacification, I studied chlorpromazine's effect on DNA; I showed that this compound induces unscheduled DNA synthesis in rat lens epithelial cells after light exposure (4), which is consistent with the above hypothesis.…”

supporting

confidence: 59%

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Jose¹

1979

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

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Phenothiazine tranquilizers are widely used pharmaceuticals that have been associated with side effects, such as formation of cataracts, that seem related to light exposure. Because patients may use them over extensive time periods, it is important to determine what deleterious cellular effects these drugs may cause and, if possible, to select or design drugs that do not cause such effects. The results reported here demonstrate that chlorinated phenothiazine drugs can be photoactivated to mutagenic species, whereas the nonchlorinated analogues do not possess this characteristic. None of the phenothiazines tested is mutagenic in the dark. Mutagenicity was observed only in strains of Salmonella typhimurium that lacked excision repair of DNA, and the mutagenicity was elevated in strains that contained the plasmid pKM101, which may enhance error-prone repair.

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supporting

confidence: 59%

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Jose¹

1979

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

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“…With respect to the mechanisms, finally leading to lens opacifications, effects on the DNA of the epithelial cells in the germinative zone and at the anterior lens pole [7,8] as well as posttranslational alterations of already ex isting protein molecules [9,10] are likely to contribute.…”

Section: Introductionmentioning

confidence: 99%

Biochemical and Morphological Changes in Rat Lenses after Long-Term UV B Irradiation

Schmidt

Schmitt²,

Kojima³

et al. 1992

Ophthalmic Res

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The aim of the present study was to investigate biochemical and morphological changes in rat lenses following long-term UV B irradiation. After an irradiation period of 156 days with follow-up documentation by means of Scheimpflug photography, section-related biochemical analyses of the lenses as well as histological investigations were performed. The video-based Scheimpflug photography (Zeiss SLC) again proved to be an excellent method for the documentation of the UV cataract induced in rats. The biochemical analyses provided indications to potential damaging mechanisms; the section-related technique used allows more precise analyses than the processing of whole lenses in a cataract type restricted to a certain layer, as is the case with UV B damage. The most prominent biochemical findings were a significant decrease in glyceraldehyde-3-phosphate dehydrogenase in the equatorial region in the group with the highest irradiation dosage and a decrease in lactate dehydrogenase in the nuclear region. The histological results reflect the local extent of the UV damage as well as its progression after a prolonged irradiation period.

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“…Other proteins were detected but have yet to be characterized in the lens epithelial cells of younger as well as aged animals. Eye lens opacification may also be ascribed to misrepair [13]. One might speculate that the alterations o f A D P ribosylation mechanisms are involved in cat aract formation.…”

Section: Discussionmentioning

confidence: 99%

“…C a 2\ M g2+-endodeoxyribonuclease, topoisomerase I, and the A D P R T itself [10][11][12], U V radiation and free radicals produce breaks in D N A and thus may increase A D P R T activity. Moreover, it has been sug gested that U V radiation and free radicals are also involved in lens aging and cataract formation [13]. Therefore, it was o f interest to follow the A D P ribosylation reaction in the lens during aging.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Protein Adenosine Diphosphate Ribosylation in Bovine Lens during Aging

Bizec¹,

Klethi²,

Mandel³

1989

Ophthalmic Res

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Adenosine diphosphate-ribosyltransferase (ADPRT) and poly-ADP-ribose glycohydrolase (poly-ADPRG) activities were investigated in the different structures of bovine lenses. These activities and protein ADP ribosylation were detected only in the lens epithelium proliferative layer. The poly-ADPR glycohydrolase activity decreased, but the poly-ADPR polymerase activity increased during aging. In lens epithelial cells of older animals, the poly-ADP-ribose level and average chain length decreased but the chain number increased. Involvement of DNA break accumulation during aging in the increase of ADPRT activity of lens epithelial cells is discussed.

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

Cited by 42 publications

References 33 publications

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Biochemical and Morphological Changes in Rat Lenses after Long-Term UV B Irradiation

Regulation of Protein Adenosine Diphosphate Ribosylation in Bovine Lens during Aging

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