Psoralen-DNA cross-linking photoadducts in dyskeratosis congenita: delay in excision and promotion of sister chromatid exchange

J Invest Dermatol. 1979 Jul;73(1):97-101. doi: 10.1111/1523-1747.ep12532783.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Chromatids / drug effects
  • Chromatids / radiation effects
  • DNA
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / radiation effects
  • Humans
  • Leukocytes / drug effects
  • Leukocytes / radiation effects
  • Male
  • Photochemotherapy
  • Skin Diseases / blood
  • Skin Diseases / congenital*
  • Skin Diseases / pathology
  • Trioxsalen / pharmacology
  • Ultraviolet Rays

Substances

  • DNA
  • Trioxsalen