CHARACTERIZATION OF MULTILOCUS LESIONS IN HUMAN-CELLS EXPOSED TO X-RADIATION AND RADON

Human TK6 lymphoblasts were exposed to X radiation or radon, and thymi dine kinase negative (TK-/-) mutants were selected, isolated and harve sted for analysis of structural changes in the TK gene. A large majori ty (82%) of the radon-induced mutants, 74% of the X-radiation-induced mutants and 45% of the spontaneous mutants lost the entire active TK a llele. To analyze these mutants further we measured the loss of hetero zygosity at several loci neighboring the TK locus on chromosome 17q. A greater proportion (61%) of the radon-induced mutants than X-radiatio n-induced or spontaneous mutants harbored the smaller lesions involvin g the TK allele alone or extending from the TK locus to one or both of the closest neighboring sequences tested. Further, 21% of the X-radia tion-induced mutants but only 5% of the radon-induced mutants lost het erozygosity at the col1A1 locus, 31 Mb from the TK gene. These results are in agreement with a recent analysis of radon- and X-radiation-ind uced lesions inactivating the HPRT gene of TK6 cells, in which we repo rted that a lower percentage of radon-than X-radiation-induced mutants showed lesions extending to markers 800 kb or more from the HPRT gene on the X chromosome (Bao et al., Mutat. Res. 326, 1-13, 1995). In the present study, we observed that the percentage of slowly growing and very slowly growing TK-/- mutants was greater after treatment with rad on than after treatment with X radiation, regardless of the type of le sion present. It is possible, therefore, that the radon-induced lesion s are complex and/or less easily repaired, leading to slow growth in a large proportion of the surviving mutant cells. (C) 1996 by Radiation Research Society