SPECTRA OF SPONTANEOUS AND X-RAY-INDUCED MUTATIONS AT THE HPRT LOCUS IN RELATED HUMAN LYMPHOBLAST CELL-LINES THAT EXPRESS WILD-TYPE OR MUTANT P53

Previous work showed that WTK1 human lymphoblastoid cells are radiores istant but more sensitive to X-ray-induced mutation than the closely r elated line TK6. In addition, WTK1 cells contain a mutant p53 while in TK6 cells p53 is wild-type. In this work, we examined the spectra of 68 X-ray-induced and 56 spontaneous mutants at the hemizygous hprt loc us in WTK1 cells. The induced spectra were classified by Southern blot and multiplex polymerase chain reaction (PCR); there were 19 point mu tations (28%) with an unaltered Southern blot or PCR pattern, 26 (38%) partial deletions or rearrangements and 23 (34%) complete gene deleti ons. The spontaneous spectrum included 25 (45%) point mutations, 22 (3 9%) partial deletions and 9 (16%) complete gene deletions. These spect ra of mutations were compared to those of TK6 cells. Although distinct differences in the spectra of mutations at the tk locus were reported previously, overall there is no significant difference in the spectra of X-ray-induced or spontaneous mutations at the hprt locus in these two cell lines. While there was an increase in the proportion of large -scale changes that occurred at tk after X irradiation, the spectrum o f mutations at the hprt locus shows all classes of mutations increasin g proportionately in WTK1 cells. However, the proportion of internal p artial deletion mutations at the hprt locus was about 2 times more fre quent in WTK1 than in TK6 cells. (C) 1995 by Radiation Research Societ y