Molecular analysis of hypoxanthine phosphoribosyltransferase gene deletions induced by α- and X-radiation in human lymphoblastoid cells

Bao, C.-Y.; Ma, A.-H.; Evans, Helen H.; Horng, Min-Fen; Mencl, J.; Hui, T.E.; Sedwick, W. David

doi:10.1016/0027-5107(94)00152-u

Cited by 56 publications

(24 citation statements)

References 41 publications

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“…Studies on the hprt locus in the human lymphoblastoid cell line TK6 (28,29) and CHO cells (30) (Tables 2, 3) differ somewhat from similar studies reported by other investigators (28)(29)(30). We find no significant difference between low-and high-LET spectra; however, when one considers whether the partial intragenic deletions involve one or multiple exons, then the spectra are significantly different from each other.…”

Section: Discussioncontrasting

confidence: 55%

Molecular Markers of Ionizing Radiation-Induced Gene Mutations in Mammalian Cells

Hsie¹,

Porter²,

Xu³

et al. 1996

Environmental Health Perspectives

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We have isolated independent Chinese hamster ovary (CHO) cell mutants at the hypoxanthine guanine phosphoribosyltransferase (hprt) locus from untreated, 60Co y-ray-exposed, and 212Bi a-exposed cells and identified the molecular changes underlying the mutation determined by multiplex polymerase chain reaction (PCR)-based exon deletion analysis. Both the parental CHO-Kl cells and the X-ray-sensitive mutant xrs-5 cells were studied. The radiosensitive xrs-5 cells are defective in DNA double-strand break rejoining ability and in V(D)J recombination, which can be complemented by Ku protein. Of the 71 spontaneous CHO-Kl hprt mutants analyzed, 78% showed no change in exon number or size, 20% showed loss of one to eight exons (partial deletion), and 3% showed loss of all nine hprt exons (total deletion). Exposure of CHO-Kl cells to 6 Gy of y rays, which reduced survival levels to 10%, produced a high deletion spectrum with 45% of the 20 mutants analyzed showing a loss of one to eight exons and 30% showing total deletion. Exposure to an equitoxic dose of cx radiation from 212Bi, a 220Rn daughter, resulted in a spectrum similar to the tray spectrum in that 75% of the 49 mutants analyzed were deletions. The cx radiation, however, tended to produce larger intragenic deletions than y radiation. Of the 92 spontaneous xrs-5 mutants analyzed for deletions, 43% showed a loss of one to eight exons and 14% showed total deletion. This suggests that, in certain regions of the hprt gene, base alterations can be converted into large deletions and alteration in the Ku protein complex can influence this type of mutational process. Exposure to ax radiation (10% survival) to xrs-5 cells resulted in a deletion spectrum similar to that seen in CHO-Kl cells. Of the 49 mutants analyzed, 43% showed no change in exon number or size, 16% showed a loss of one to eight exons, and 41 % showed total deletion. While the defect in xrs-5 cells has a profound effect on spontaneous mutant spectra, this defect does not appear to affect a-induced mutation spectra. EnvironHealth Perspect 104(Suppl 3): 675-678 (1996)

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Section: Discussioncontrasting

confidence: 55%

Molecular Markers of Ionizing Radiation-Induced Gene Mutations in Mammalian Cells

Hsie¹,

Porter²,

Xu³

et al. 1996

Environmental Health Perspectives

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“…It is often reported that the frequency of deletion is higher for high LET radiation than for low LET radiation (Schwartz et al, 1994;Stoll et al, 1995;Zhu et al, 1995;Suzuki et al, 1996). On the contrary, some researchers reported that no significant difference on the frequency of deletions was observed between high LET and low LET radiation-induced mutants (Thacker, 1986;Aghamohammadi et al, 1992;Jostes et al, 1994, Bao et al, 1995Yamada et al, 1996). The reason for the apparent contradiction remains to be elucidated.…”

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confidence: 99%

Molecular analysis of carbon ion-induced mutations in Arabidopsis thaliana.

et al. 1998

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In order to elucidate the characteristics of the mutations induced by ion particles at the molecular level in plants, mutated loci in carbon ion-induced mutants of Arabidopsis were investigated by PCR and Southern blot analyses. In the present study, two lines of gl1 mutant and two lines of tt4 mutant were isolated after carbon ion-irradiation. Out of four mutants, one had a deletion, other two contained rearrangements, and one had a point-like mutation. From the present result, it was suggested that ion particles induced different kinds of alterations of the DNA and therefore they could produce various types of mutant alleles in plants.

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“…This phenomenon is true for both proliferating human lymphoblastoid cells [Bao et al, 1995] and proliferating primary fibroblasts [Yamada et al, 1996], as well as G 0 T lymphocytes [O'Neill et al, 1990b;Mognato et al, 2001]. The Magnato et al [2001] study also showed a dose-related increase in deletion mutations up to 3 Gy exposure, but did not report patterns consistent with gene rearrangements.…”

Section: à6mentioning

confidence: 87%

In vitro studies of the genotoxicity of ionizing radiation in human G0 T lymphocytes

O’Neill

Nicklas

Hirsch

et al. 2005

Environ. Mol. Mutagen.

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In an effort to mimic human in vivo exposures to ionizing irradiation, G(0) phase T lymphocytes from human peripheral blood samples were utilized for in vitro studies of the genotoxic effects of (137)Cs low-LET irradiation and (222)Rn high-LET irradiation. Both types of radiation induced mutations in the HPRT gene in a dose-dependent manner, with a mutant frequency (MF) = 4.28 + 1.34x + 7.51x(2) for (137)Cs (R(2) = 0.95) and MF = 4.81 + 0.67x for (222)Rn (R(2) = 0.51). Post (137)Cs irradiation incubation in the presence of cytosine arabinoside, a reversible inhibitor of DNA repair, caused an increase in the MF over irradiation alone, consistent with a misrepair mechanism being involved in the mutagenicity of low-LET irradiation. The spectrum of (137)Cs irradiation-induced mutation displayed an increase in macro-deletions (in particular total gene deletions) and rearrangement events, some of which were further defined by either chromosome painting or direct DNA sequencing. The spectrum of (222)Rn irradiation-induced mutation was characterized by an increase in small alterations, especially multiple single base deletions/substitutions and micro-deletions. These studies define the specific response of human peripheral blood T cells to ionizing irradiation in vitro and form a basis for evaluating the genotoxic effects of human in vivo exposure.

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Molecular analysis of hypoxanthine phosphoribosyltransferase gene deletions induced by α- and X-radiation in human lymphoblastoid cells

Cited by 56 publications

References 41 publications

Molecular Markers of Ionizing Radiation-Induced Gene Mutations in Mammalian Cells

Molecular Markers of Ionizing Radiation-Induced Gene Mutations in Mammalian Cells

Molecular analysis of carbon ion-induced mutations in Arabidopsis thaliana.

In vitro studies of the genotoxicity of ionizing radiation in human G0 T lymphocytes

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