“Unscheduled” DNA synthesis in lens epithelium following ultraviolet irradiation

During early embryonic life the lens becomes an autonomous organ system containing the proliferating cells which are the sole contributors to its growth; the lens becomes topographically divided into proliferative (epithelium) and nonproliferative (fiber) compartments (see, for review Cleaver [1]). In nondividing lens fibers, cell nuclei progressively lose DNA, degenerate and disappear [9]. Modak [8] and Modak and Unger-Ullman [10] that terminally differentiating and aging postmitotic cells accumulate lesions in their DNA due to defective DNA repair enzyme machinery. We have shown earlier [2] that as lens fiber cells differentiate there occurs a decrease in the rejoining capacity for single strand breaks in DNA. A precise analysis of DNA repair capacity in the entire lens, or in the epithelium, is hampered by the fact that during two-thirds of the developmental period the cell population increases rapidly [11]. Thus, to demonstrate DNA repair activity, it is necessary to suppress the normal cell division. To this end, we undertook the analysis of thymidine incorporation in the presence of hydroxyurea, a drug known [1] to inhibit scheduled DNA synthesis but not repair synthesis. Our data show that the drug does suppress the incorporation of ³H-thymidine initially, it also causes stimulation of incorporation during the later phase. Similar to the rabbit lens epithelium [4], the central epithelium from adult bovine lenses has a very low mitotic index [Tréton et al., unpubl.] indicative of a near total lack of cell proliferative activity. In these, we observe ultraviolet-induced ³H-thymidine incorporation without the use of hydroxyurea. We also find that protofibers carry out unscheduled DNA synthesis similar to those in rat lens [6].

Section: Discussionsupporting

confidence: 78%

“…In these, we observe ultraviolet-induced :,H-thymidine in corporation without the use of hydroxyurea. We also find that protofibers carry out un scheduled DNA synthesis similar to those in rat lens [6]. …”

mentioning

confidence: 53%

DNA Repair in the Lens

Tréton¹,

Modak²,

Courtois³

1979

“…By means of autoradiography, DNA repair synthesis may also be observed in the terminally differentiated cells in the meridional rows [22], suggesting the importance of DNA repair for normal metabolism in the lens.…”

Section: Dna Repair In the Lensmentioning

confidence: 99%

“…Using autoradiographic techniques, we have observed unscheduled DNA synthesis in epithelial cells in organ-cultured lenses following ultraviolet (254 nm maximum) irradiation [22]; and Counis et al [13] have also observed repair synthesis in lens cells in tissue culture following X-irradiation. By means of autoradiography, DNA repair synthesis may also be observed in the terminally differentiated cells in the meridional rows [22], suggesting the importance of DNA repair for normal metabolism in the lens.…”

Section: Dna Repair In the Lensmentioning

confidence: 99%

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

Jose

1978

Self Cite

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.

“…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

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.