title: UV-B-induced DNA damage and repair in the mouse lens.
abstract: OBJECTIVE
  Epidemiologic studies have linked UV-B exposure to development of cortical cataracts, but the underlying molecular mechanism(s) is unresolved. Here, we used a mouse model to examine the nature and distribution of DNA photolesions produced by ocular UV-B irradiation.
  
  
  METHODS
  Anesthetized mice, eye globes, or isolated lenses were exposed to UV-B. Antibodies specific for 6-4 photoproducts (6-4 PPs) or cyclobutane pyrimidine dimers (CPDs) were used to visualize DNA adducts.
  
  
  RESULTS
  Illumination of intact globes with UV-B-induced 6-4 PP and CPD formation in cells of the cornea, anterior iris, and central lens epithelium. Photolesions were not detected in retina or lens cells situated in the shadow of the iris. Photolesions in lens epithelial cells were produced with radiant exposures significantly below the minimal erythemal dose. Lens epithelial cells rapidly repaired 6-4 PPs, but CPD levels did not markedly diminish, even over extended postirradiation recovery periods in vitro or in vivo. The repair of 6-4 PPs did not depend on the proliferative activity of the epithelial cells, since the repair rate in the mitotically-active germinative zone (GZ) was indistinguishable from that of quiescent cells in the central epithelium.
  
  
  CONCLUSIONS
  Even relatively modest exposures to UV-B produced 6-4 PP and CPD photolesions in lens epithelial cells. Cyclobutane pyrimidine dimer lesions were particularly prevalent and were repaired slowly if at all. Studies on sun-exposed skin have established a causal connection between photolesions and so-called UV-signature mutations. If similar mechanisms apply in the lens, it suggests that somatic mutations in lens epithelial cells may contribute to the development of cortical cataracts.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri.
authors.forename: Rosana
authors.initials: R
authors.lastname: Mesa
authors.forename: Steven
authors.initials: S
authors.lastname: Bassnett
mesh_terms: D000818:Animals; D002386:Cataract / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D004195:Disease Models, Animal; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D014466:Ultraviolet Rays / Q000009:adverse effects*
keywords: DNA damage; UV-B; cortical cataract
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