title: Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer-prone syndromes.
abstract: Host-cell reactivation (HCR) 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.
authors.affiliation: MGC-Department of Molecular Cell Biology, Laboratory for Molecular Carcinogenesis, Leiden University Medical Centre, Netherlands. abrahams@rullf2.medfac.leidenuniv.nl
authors.forename: P J
authors.initials: PJ
authors.lastname: Abrahams
authors.forename: A
authors.initials: A
authors.lastname: Houweling
authors.forename: P D
authors.initials: PD
authors.lastname: Cornelissen-Steijger
authors.forename: N G
authors.initials: NG
authors.lastname: Jaspers
authors.forename: F
authors.initials: F
authors.lastname: Darroudi
authors.forename: C M
authors.initials: CM
authors.lastname: Meijers
authors.forename: L H
authors.initials: LH
authors.lastname: Mullenders
authors.forename: R
authors.initials: R
authors.lastname: Filon
authors.forename: F
authors.initials: F
authors.lastname: Arwert
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: A P
authors.initials: AP
authors.lastname: Natarajan
authors.forename: C
authors.initials: C
authors.lastname: Terleth
authors.forename: A A
authors.initials: AA
authors.lastname: Van Zeeland
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Eb
mesh_terms: D015783:Aniridia / Q000235:genetics / Q000378:metabolism / Q000821:virology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D004416:Dysplastic Nevus Syndrome / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005057:Eukaryotic Cells / Q000378:metabolism / Q000528:radiation effects / Q000821:virology; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016158:Genes, p53 / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D010375:Pedigree; D012867:Skin / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000528:radiation effects; D006623:von Hippel-Lindau Disease / Q000235:genetics / Q000378:metabolism / Q000821:virology