TY - JOUR
T1 - Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer-prone syndromes
AU - Abrahams, Peter J.
AU - Houweling, Ada
AU - Cornelissen-Steijger, Paulien D M
AU - Jaspers, Nicolaas G J
AU - Darroudi, Firouz
AU - Meijers, Caro M.
AU - Mullenders, Leon H F
AU - Filon, Ronald
AU - Arwert, Fré
AU - Pinedo, Herbert M.
AU - Natarajan, Adaya Palam T
AU - Terleth, Carrol
AU - Van Zeeland, Albert A.
AU - Van Der Eb, Alex J.
PY - 1998/3
Y1 - 1998/3
N2 - 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.
AB - 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.
KW - Genome overall and gene-specific DNA repair
KW - Hereditary cancer-prone syndrome
KW - Host-cell reactivation of herpes simplex virus type 1
KW - Sister chromatid exchange
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U2 - 10.1016/S0921-8777(98)00009-3
DO - 10.1016/S0921-8777(98)00009-3
M3 - Article
C2 - 9637247
AN - SCOPUS:0031778366
SN - 0921-8777
VL - 407
SP - 189
EP - 201
JO - Mutation Research - DNA Repair
JF - Mutation Research - DNA Repair
IS - 2
ER -