Persistent genetic instability induced by synergistic interaction between x-irradiation and 6-thioguanine
- Univ. of California, Riverside, CA (United States); and others
Clonal karyotypic analysis was performed using G-banding on four groups of clones derived from TK6 human lymphoblasts: 25 HPRT{sup {minus}} total gene deletion mutants induced by exposure to 2 Gy of x-rays; 8 spontaneous HPRT{sup {minus}} total gene deletion mutants; 25 clones irradiated with 2 Gy, not selected with 6-thioguanine. Ten to twenty metaphases were examined for each clone. Extensive karyotypic heterogeneity was observed among x-ray induced HPRT {sup {minus}} mutants involving translocations, deletions, duplications and aneuploidy; recovery of chromosomal aberrations and karyotypic heterogeneity was greater than the additive effects of clones treated with x-irradiation or 6-thioguanine alone. This synergistic interaction between x-irradiation and 6-thioguanine was observed despite a 7 day phenotypic expression interval between exposure to the two agents. Thus, x-irradiated TK6 cells appear to be persistently hypersensitive to the induction of genetic instability. Several mutants appeared to exhibit evidence of clonal evolution since aberrant chromosomes observed in one metaphase, were found to be further modified in other metaphases. In order to determine if genetic instability, identified by clonal karyotypic heterogeneity, affected specific locus mutation rates, we utilized the heterozygous thymidine kinase (tk) locus as a genetic marker. Four x-ray induced HPRT{sup {minus}} mutants with extensive karyotypic heterogeneity, exhibited mutation rates at tk ranging from 5 to 8 fold higher than the parental TK6 cells. Further analysis, using fractionated low dose radiation exposure, is currently in progress.
- OSTI ID:
- 115126
- Report Number(s):
- CONF-9503160-; ISSN 0893-6692; TRN: 95:023010
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 25, Issue Suppl.25; Conference: 26. annual Environmental Mutagen Society meeting, St. Louis, MO (United States), 12-16 Mar 1995; Other Information: PBD: 1995
- Country of Publication:
- United States
- Language:
- English
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