Reduced Capacity to Repair Irradiated Adenovirus in Fibroblasts from Xeroderma Pigmentosum Hétérozygotes1

Xeroderma pigmentosum (XP) is one of a number of autosomal recessive syndromes in humans characterized by a marked predisposition to cancer. Fibroblasts from these pa tients show a defect in DMA repair. The XP hétérozygotes 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 hétérozygotes was examined using a sensitive host cell reactivation technique. Unirradiated and irradiated suspensions of adenovirus type 2 (Ad 2) were as sayed for their ability to form viral structural antigens in fibroblasts from XP hétérozygotes, XP homozygotes, and normals. A reduced host cell reactivation (of viral structural antigen production) for both ultravioletand y-irradiated Ad 2 was detected in four XP hétérozygotes representing three different complementation groups as well as their XP homozygous chil dren. 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 y-irradiated Ad 2. These results add further support to a direct relationship be tween cancer proneness and DNA repair defects and show the merits of this host cell reactivation technique in identifying XP hétérozygotes. Identification of XP hétérozygotes i of consid erable public health interest not only in genetic counseling but also in the prevention of cancer.