RADIOSENSITIVITY OF ATAXIA-TELANGIECTASIA, X-LINKED AGAMMAGLOBULINEMIA, AND RELATED SYNDROMES USING A MODIFIED COLONY SURVIVAL ASSAY

We used a modified colony survival assay to measure the sensitivity to ionizing radiation of more than 50 lymphoblastoid cell lines from nor mal individuals and from patients with ataxia-telangiectasia, Nijmegen breakage syndrome variants, and X-linked agammaglobulinemia. All of t hese disorders are associated with an increased frequency of cancer. L ymphoblastoid cell lines from patients with ataxia-telangiectasia comp lementation groups A, C, D, and E; AT(Fresno); Nijmegen breakage syndr ome variants V1 and V2; and X-linked agammaglobulinemia showed marked radiosensitivity, whereas ataxia-telangiectasia heterozygotes were sim ilar to controls. Friedreich's ataxia is not associated with increased cancer risk; lymphoblastoid cell lines from two such patients showed normal radiosensitivity. Taken together, these results suggest that so me forms of X-ray sensitivity and cancer susceptibility share a common mechanism, such as an enzyme that is necessary both for the repair of radiation damage to DNA and for gene rearrangements during V(D)J reco mbination.