IMPAIRED DNA-REPAIR CAPACITY IN SKIN FIBROBLASTS FROM VARIOUS HEREDITARY CANCER-PRONE SYNDROMES

Host-cell reactivation (HCR) of UV-C-irradiated herpes simplex virus t ype 1 (HSV-1) has been determined in skin fibroblasts from the followi ng 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 reduce d HCR in all cases where the cells were derived from persons carrying one mutated p53 allele, whereas cells derived from members with two wi ld-type alleles show normal HCR. LFS cells with reduced HCR also revea l 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 H CR is observed in skin fibroblasts derived from both afflicted and una ffected individuals. In addition, these cells display lower survival a fter exposure to UV-C and exhibit higher levels of SCEs than those in normal cells. These observations indicate that various hereditary canc er-prone syndromes, carrying mutations in different tumor-suppressor g enes, exhibit an unexplained impairment of the capacity to repair UV-d amaged DNA. (C) 1998 Elsevier Science B.V.