DNA Repair in the Lens

Abstract

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].

X‐RAY EFFECTS ON LENS DNA — IMPLICATIONS OF SUPEROXIDE(O2·‐)

“…These observation also raise the question of the variation in the efficacy of the DNA repair system from centre to the periphery. Unfortunately, the knowledge about the activity of repair enzymes in the lens is very obscure (Treton et al 1979). Since lens is transparent, the existence of such a rapair system will be of great physiological significance in protecting DNA molecule from damage due to continued photo catalytic generation of Oi-.…”