Molecular basis of X-ray-induced mutation at the HPRT locus in human lumphocytes

Skulimowski, Anna; Turner, David R.; Morley, Alexander A.; Sanderson, Barbara J.S.; Haliandros, Marina

doi:10.1016/0027-5107(86)90075-8

Cited by 46 publications

(6 citation statements)

References 12 publications

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“…Alternatively, WS cells might mimic the effects of x-and y-irradiation by producing high endogenous levels of reactive oxygen intermediates (21). This intriguing possibility is suggested by the high proportion of deletions seen in collections of x-and y-ray-induced HPRT mutations (21)(22)(23)(24). X-and y-radiation can also induce cytogenetic changes that occur spontaneously at high frequency in WS cells (5,25) and the premature appearance of selected features of aging (26).…”

Section: Discussionmentioning

confidence: 99%

Mutator phenotype of Werner syndrome is characterized by extensive deletions.

Fukuchi

Martin

Monnat

1989

Proc. Natl. Acad. Sci. U.S.A.

393

240

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Section: Discussionmentioning

confidence: 99%

Mutator phenotype of Werner syndrome is characterized by extensive deletions.

Fukuchi

Martin

Monnat

1989

Proc. Natl. Acad. Sci. U.S.A.

393

240

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“…This increase is approximately one-half of that observed in lymphocytes after 2-2.5 Gy irradiation in vitro [Sanderson et al, 19841. Provided 50% of the induced mutants possess gross alterations (52% of mutants possessed gross alterations after 3 Gy in vitro irradiation as reported by Skulimowski et al in 1986), the frequency of such alterations will be 30-40% in these people. The results for survivor JS (26%) is somewhat lower, but compatible with this estimation.…”

Section: Discussionmentioning

confidence: 96%

Molecular analyses of in vivo hprt mutant T cells from atomic bomb survivors

Hakoda

Hirai

Kyoizumi

et al. 1989

Environ and Mol Mutagen

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In vivo-derived hprt-deficient mutant T cells isolated from three nonirradiated controls and two atomic bomb survivors were studied by Southern blot analysis to investigate the molecular spectra of the mutations. Mutant frequencies for the three controls were 1.8, 2.3, and 7.3 x 10(-6), and those for the two survivors (who had received radiation doses of 2.46 and 2.15 Gy, based upon the revised atomic bomb shielded kerma estimates) were 9.3 and 14.4 x 10(-6), respectively. Fourteen (13%) of 105 mutant T-cell colonies from the controls showed various structural changes in the hprt gene. The frequency of mutants with hprt gene structural changes in one atomic bomb survivor, who exhibited a mutant frequency of 9.3 x 10(-6), was 26% (16/61), which was significantly higher than that of the controls. However, the frequency of structural changes in the other survivor (14%, 8/59) was not higher than that of the controls. Two sets of mutants (in total, eight mutants) from the survivor, who showed a significantly higher frequency of mutants with hprt gross alterations than did the controls, had the same hprt changes and the same rearrangements of T-cell receptor (TcR) beta- and gamma-chain genes, indicating a clonal expansion from one progenitor mutant. This phenomenon may reflect an in vivo recovery process of T cells in the periphery after exposure to atomic bomb radiation. However, when comparing the frequency of mutations, these two sets of mutants should be reduced. After reducing the total number of mutants from the number of gross hprt changes, the frequency was not significantly higher than that of the controls.

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“…There were certain differences in the spectrum of changes observed in spontaneous and induced mutants of human cells in culture when compared with those seen in rodent cells (see Table I) (Skulimowski et al, 1986;Liber et al, 1987). In human cells there were relatively more radiationinduced mutants which showed no detectable change in gene organization and more spontaneous mutants which had totally lost the hprt gene than in rodent cells.…”

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confidence: 97%

“…However, the study by Meuth's laboratory ) characterized mutants at both aprt and hprt loci as well as determined changes in the DNA sequence. These studies show that there are locus specific effects influencing the type of mutation seen. hprt locus The alterations in gene structure induced by ionizing radiation at the hprt locus have been determined at the level of restriction fragment length changes in Chinese hamster V79 cells (Vrieling et al, 1985;Fuscoe, et al, 1986), CHO cells Stankowski & Hsie, 1986;, and human lymphocytes (Skulimowski et al, 1986;Liber et al, 1987) (see Table I). The limit of resolution is 500 bp.…”

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confidence: 99%