Analysis of Radiation Hypersensitivity of Human Cells From Genetic Disease by the use of Chromosome Transfer

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The chromosomal localization of the gene which complements radiation hypersensitivity of AT(ataxia telangiectasia)cells was studied by microcell-mediated chromosome transfer.1. An immortalized AT cell line, AT2KYSV, aDd its 6-thioguanineresistant derivative, AT2KYSVTG, were used as recipients. Five strains of mouse A9 cells carrying a single human chromosome were used as chromosome donors. The chromosomes carried were PSV2neo-tagged human chromosome 11, X chromosome, or X/11 recombinant chromosomes containing either llpter-ql3, llpter-q23 or llpll-qter.2. Among seven G418-resistant microcell hybrids obtained from the transfer of a PSV2neo-tagged chromosome 11, three clones showed restoration of radiation resistance with concomitant gain of an extra chromosome 11, while the others contained no recognizable or deleted chromosome 11.3. The HAT-resistant microcell hybrids obtained from the transfer of an intact X chromosome or an X/11 chromosome bearing the Ilpter-ql3 region did not show a diffprence in radiosensitivity from parental AT cells, while those obtained from the transfer of X/11 chromosomes bearing either the llpll-qter or Ilpter-q23 region exhibited a marked radioresistance.4. A HAT-resistant but radiosensitive variant was further obtained from the microcell fusion with an A9 strain carrying an X/11 chromosome bearing llpll-qter region, in which a deletion at the llq23 region was found. The results indicate that the gene which complements a radiosensitive phenotype of AT is located at the q23 region of chromosome 11. The derivative chromosome 11 found here to be associated with concomitant loss of the AT locus or its function would be useful for the molecular dissection of the llq23 region with relevance to the AT gene.