Quantification of thioguanine-resistant lymphocytes from mice irradiated in vivo.

Lorenz, R.; Gollner, Thomas; Hempel, Klaus

doi:10.1289/ehp.9088129

Cited by 7 publications

(2 citation statements)

References 15 publications

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“…Irradiation (6,19), and to a lesser extent, alkylating agents (9,10), have been shown to increase FMC. Azathioprine also can induce somatic mutations.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Clinical Parameters Associated with Increased Frequency of Mutant T Cells in Patients with Systemic Lupus Erythematosus

Dawisha¹,

Gmelig-Meyling²,

Steinberg³

1994

Arthritis & Rheumatism

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Objective. To determine the clinical features that contribute to an increased frequency of mutant T cells (FMC) in patients with systemic lupus erythematosus (SLE).Methods. During in vivo T cell division, there are errors in replication which give rise to mutations throughout the genome. An estimate of such mutations may be obtained by focusing on mutations in the hprt gene, which can be screened by assessing relative growth of T cell clones in the presence and absence of 6-thioguanine. In this study, peripheral blood T cell clones from 47 patients with SLE were assessed, and the frequency of mutant T cells (FMC) determined. An attempt was made to correlate the FMC with disease measures.Results. Patients with SLE had a spectrum of FMC values, ranging from normal to almost 1,000 times normal. Total duration of active disease (r, = 0.94), past highest disease activity index (r, = 0.80), and number of lupus flares (r, = 0.76) correlated most strongly (P < 0.0001) with FMC by Spearman's rank order analysis. In contrast, current disease activity index and current anti-DNA level did not correlate with FMC. Similar correlations between FMC I and cumulative past lupus disease activity were found by linear regression analysis (rp = 0.89 for the correlation between the natural From the Arthritis and Rheumatism Branch, NIAMS, NIH,

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“…Irradiation (6,19), and to a lesser extent, alkylating agents (9,10), have been shown to increase FMC. Azathioprine also can induce somatic mutations.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Clinical Parameters Associated with Increased Frequency of Mutant T Cells in Patients with Systemic Lupus Erythematosus

Dawisha¹,

Gmelig-Meyling²,

Steinberg³

1994

Arthritis & Rheumatism

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“…The occurrence of dosedependent radiation mutagenesis in mice has been demonstrated in a number of studies [Dempsey and Morley 1986;Lorenz et al, 1990Lorenz et al, , 1993Lorenz et al, , 1994Grdina et al, 1992;Kataoka et al, 1992Kataoka et al, , 1993Gaziev et al, 1995;Klarmann et al, 1995;Dobrovolsky et al, 2002;Liang et al, 2007]. However, the more extensive evaluation of time elapsed after acute g irradiation revealed that mutant frequency dependence on dose shifted between 3 and 5 weeks and 10-53 weeks, from being clearly quadratic at the peak of mutant recovery in weeks 3-5 to a statistically strong but less-defined dose relationship in the later time frame.…”

Section: Discussionmentioning

confidence: 99%

Studies of thioguanine‐resistant lymphocytes induced by in vivo irradiation of mice

Jones

Burkhart-Schultz

Strout

et al. 2008

Environ and Mol Mutagen

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The frequency of Hprt-deficient lymphocytes in mice after in vivo gamma irradiation, has been found to vary as a function of time elapsed after exposure and irradiation dose. The frequency of mutant lymphocytes in spleen was determined using an in vitro, clonogenic assay for thioguanine-resistant T-lymphocytes. Mice were exposed to single doses of 0-400 cGy from cesium-137 or to eight daily doses of 50 cGy. The time to maximum-induced mutant frequency was 3 weeks. The dose response was strikingly curvilinear at 3-5 weeks after irradiation, but less precisely defined for 10-53 weeks after exposure, being fit by either linear or quadratic dependence. Three weeks after eight daily 50 cGy exposures, mutant frequency was elevated above controls and mice exposed to 50 cGy (which were not distinct from the nonirradiated controls), but only 17% in that of mice given a single 400 cGy fraction. This fractionation effect and the curvilinearity of the early dose-response curve suggested that saturation of repair increased the yield of mutations at higher acute doses. The decline of spleen mutant frequency in mice observed between 5 and 10 weeks after irradiation may reflect selection against some mutants. The marked variation of mutant frequency, as a function of time after irradiation and of dose rate, emphasize the need to evaluate these variables carefully and consistently in future studies.

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Isolation and quantification of class 1 MHC gene mutants in mouse T cells by immunoselection with a magnetic cell sorter (MACS)

Wixler¹,

Klarmann²,

Begemann³

et al. 1994

Journal of Immunological Methods

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Quantification of thioguanine-resistant lymphocytes from mice irradiated in vivo.

Cited by 7 publications

References 15 publications

Assessment of Clinical Parameters Associated with Increased Frequency of Mutant T Cells in Patients with Systemic Lupus Erythematosus

Assessment of Clinical Parameters Associated with Increased Frequency of Mutant T Cells in Patients with Systemic Lupus Erythematosus

Studies of thioguanine‐resistant lymphocytes induced by in vivo irradiation of mice

Isolation and quantification of class 1 MHC gene mutants in mouse T cells by immunoselection with a magnetic cell sorter (MACS)

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