title: Reduced capacity to repair irradiated adenovirus in fibroblasts from xeroderma pigmentosum heterozygotes.
abstract: Xeroderma pigmentosum (XP) is one of a number of autosomal recessive syndromes in humans characterized by a marked predisposition to cancer. Fibroblasts from these patients show a defect in DNA repair. The XP heterozygotes also show elevated skin cancer incidence, but reports concerning their DNA repair capacity are conflicting. In this study, the DNA repair capacity of four XP heterozygotes was examined using a sensitive host cell reactivation technique. Unirradiated and irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens in fibroblasts from XP heterozygotes, XP homozygotes, and normals. A reduced host cell reactivation (of viral structural antigen production) for both ultraviolet- and gamma-irradiated Ad 2 was detected in four XP heterozygotes representing three different complementation groups as well as their XP homozygous children. The doses necessary to reduce the survival of viral structural antigen production by irradiated AD 2 to 37% in the XP heterozygous strains were expressed as a percentage of that obtained in normal strains and ranged from 55 to 82% for ultraviolet-irradiated Ad 2 and 71 to 79% for gamma-irradiated Ad 2. These results add further support to a direct relationship between cancer proneness and DNA repair defects and show the merits of this host cell reactivation technique in identifying XP heterozygotes. Identification of XP heterozygotes is of considerable public health interest not only in genetic counseling but also in the prevention of cancer.
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics; D004260:DNA Repair; D004279:DNA, Viral / Q000378:metabolism* / Q000528:radiation effects; D005720:Gamma Rays; D006579:Heterozygote; D006801:Humans; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000503:physiopathology*
chemical_list: D004279:DNA, Viral