title: Psoralen-DNA cross-linking photoadducts in dyskeratosis congenita: delay in excision and promotion of sister chromatid exchange.
abstract: Dyskeratosis congenita is a rare X-linked recessive disease, characterized by mucosal leukokeratosis, nail dystrophy, telangiectasia, reticulated hyperpigmentation, pancytopenia, and a heightened susceptibility to infection and malignancy. We exposed cultured fibroblasts and peripheral leukocytes from normal persons and from 2 unrelated young adult men with dyskeratosis congenita to 4,5',8-trimethylpsoralen and ultraviolet light. We than compared certain of their responses. Labeled DNA from fibroblasts exposed to 4,5',8-trimethylpsoralen and ultraviolet light showed fast-sedimenting DNA, a pattern we interpreted as evidence that cross-linking, psoralen-DNA photoadducts had been formed by the treatment. Fast-sedimenting DNA persisted for 24 hr in dyskeratosis congenita cells but disappeared from normal cells during a 24-hr repair period. Cultured peripheral blood leukocytes from persons with this syndrome similarly exposed to 4,5',8-trimethylpsoralen and ultraviolet light developed more sister chromatid exchanges than did cells from normal persons. These data suggest that a heightened susceptibility in DNA cross-links may be of fundamental importance in the etiology of dyskeratosis congenita.
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002842:Chromatids / Q000187:drug effects / Q000528:radiation effects; D004247:DNA; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D010778:Photochemotherapy; D012871:Skin Diseases / Q000097:blood / Q000151:congenital* / Q000473:pathology; D014307:Trioxsalen / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D004247:DNA; D014307:Trioxsalen