Original Article

Journal of Investigative Dermatology (1979) 73, 97–101; doi:10.1111/1523-1747.ep12532783

Psoralen-DNA Cross-linking Photoadducts in Dyskeratosis Congenita: Delay in Excision and Promotion of Sister Chromatid Exchange

D Martin Carter, Mary Pan, Alan Gaynor, Joseph S McGuire and Laurence Sibrack

Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.

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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 then 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 to DNA cross-links may be of fundamental importance in the etiology of dyskeratosis congenita.

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