Characterization of multilocus lesions in human cells exposed to X radiation and radon.
Human TK6 lymphoblasts were exposed to X radiation or radon, and thymidine kinase negative (TK-/-) mutants were selected, isolated and harvested for analysis of structural changes in the TK gene. A large majority (82%) of the radon-induced mutants, 74% of the X-radiation-induced mutants and 45% of the spontaneous mutants lost the entire active TK allele. To analyze these mutants further we measured the loss of heterozygosity at several loci neighboring the TK locus on chromosome 17q. A greater proportion (61%) of the radon-induced mutants than X-radiation-induced or spontaneous mutants harbored the smaller lesions involving 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-radiation-induced mutants but only 5% of the radon-induced mutants lost heterozygosity at the col1A1 locus, 31 Mb from the TK gene. These results are in agreement with a recent analysis of radon- and X-radiation-induced lesions inactivating the HPRT gene of TK6 cells, in which we reported 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 radon than after treatment with X radiation, regardless of the type of lesion present. It is possible, therefore, that the radon-induced lesions are complex and/or less easily repaired, leading to slow growth in a large proportion of the surviving mutant cells.
Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106-4942, USA.
M A
MA
Chaudhry
Q
Q
Jiang
M
M
Ricanati
M F
MF
Horng
H H
HH
Evans
D001402:B-Lymphocytes; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000528:radiation effects; D017931:DNA Primers; D004307:Dose-Response Relationship, Radiation; D005796:Genes / Q000528:radiation effects*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011886:Radon; D013937:Thymidine Kinase / Q000172:deficiency / Q000235:genetics*; D014965:X-Rays
D017931:DNA Primers; D013937:Thymidine Kinase; D011886:Radon