Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer-prone syndromes

Peter J. Abrahams, Ada Houweling, Paulien D M Cornelissen-Steijger, Nicolaas G J Jaspers, Firouz Darroudi, Caro M. Meijers, Leon H F Mullenders, Ronald Filon, Fré Arwert, Herbert M. Pinedo, Adaya Palam T Natarajan, Carrol Terleth, Albert A. Van Zeeland, Alex J. Van Der Eb

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Host-cell reactivation (NCR) of UV-C-irradiated herpes simplex virus type 1 (HSV-1) has been determined in skin fibroblasts from the following hereditary cancer-prone syndromes: aniridia (AN), dysplastic nevus syndrome (DNS), Von Hippel-Lindau syndrome (VHL), Li-Fraumeni syndrome (LFS) and a family with high incidence of breast and ovarian cancer. Cells from AN, DNS or VHL patients were found to exhibit heterogeneity in HCR. Cells from individuals belonging to an LFS family show reduced HCR in all cases where the cells were derived from persons carrying one mutated p53 allele, whereas cells derived from members with two wild-type alleles show normal HCR. LFS cells with reduced HCR also reveal reduced genome overall repair, and a slower gene-specific repair of the active adenosine deaminase (ADA) gene, but little if any repair of the inactive 754 gene. In the breast/ovarian cancer family, reduced HCR is observed in skin fibroblasts derived from both afflicted and unaffected individuals. In addition, these cells display lower survival after exposure to UV-C and exhibit higher levels of SCEs than those in normal cells. These observations indicate that various hereditary cancer-prone syndromes, carrying mutations in different tumor-suppressor genes, exhibit an unexplained impairment of the capacity to repair UV-damaged DNA.

Original languageEnglish (US)
Pages (from-to)189-201
Number of pages13
JournalMutation Research - DNA Repair
Issue number2
StatePublished - Mar 1998
Externally publishedYes


  • Genome overall and gene-specific DNA repair
  • Hereditary cancer-prone syndrome
  • Host-cell reactivation of herpes simplex virus type 1
  • Sister chromatid exchange

ASJC Scopus subject areas

  • Toxicology
  • Genetics
  • Molecular Biology


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