In vivo sister-chromatid exchange: A sensitive measure of DNA damage

Nakanishi, Yoshifumi; Schneider, Edward L.

doi:10.1016/0027-5107(79)90023-x

Cited by 122 publications

(44 citation statements)

References 29 publications

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“…Such an explanation has been proposed for the relationship between the high levels of spontaneous SCE and increased tumor frequency in Bloom's syndrome (Tice et al, 1978). It has been shown that agents that induce SCE can also be clastogenic and induce gene mutations, although the DNA lesions that lead to these endpoints may differ (Carranoet al 1978: Nakanishi andSchneider. 1979).…”

Section: Resultsmentioning

confidence: 99%

A comparison of sister chromatid exchange frequencies in peripheral lymphocytes and bone marrow cells of Fischer 344 and Sprague-Dawley rats

Dearfield¹,

Jacobson‐Kram²,

Williams³

1984

Cytogenet Genome Res

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We have investigated spontaneous sister chromatid exchange (SCE) frequencies in peripheral lymphocytes and bone marrow cells explanted from two strains of the laboratory rat, Fischer 344 and Sprague-Dawley. A small, but significant difference was noted for both cell types, with the Fischer 344 rat being consistently higher. Other cell parameters, such as the mitotic index and the replicative index, were similar in the two strains. SCE levels in cultured peripheral lymphocytes after intraperitoneal administration of the alkylating drug cyclophosphamide (10 mg/kg) were similar for the two strains. Fischer 344 rats are known to have approximately a 10-fold higher incidence of spontaneous leukemia than do Sprague-Dawley rats. Since SCE frequency is a sensitive measure of DNA damage, our observations suggest that high leukemia incidence in the Fischer 344 rat may be related to a higher level of spontaneous DNA damage.

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Section: Resultsmentioning

confidence: 99%

A comparison of sister chromatid exchange frequencies in peripheral lymphocytes and bone marrow cells of Fischer 344 and Sprague-Dawley rats

Dearfield¹,

Jacobson‐Kram²,

Williams³

1984

Cytogenet Genome Res

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“…Although recognized for over 50 y (25), their biological significance remains neither fully understood nor appreciated. SCE are induced by DNA-damaging agents that block DNA replication (26), and can lead to deletions, translocations, and loss of heterozygosity (27), manifestations of genomic instability and precursors of carcinogenesis. These adverse outcomes likely originate from an inability to resolve replication forks stalled at sites of DNA damage, whereupon SCE provides a means to "bypass" the damage (28).…”

mentioning

confidence: 99%

Hyper telomere recombination accelerates replicative senescence and may promote premature aging

Hagelstrom

Blagoev

Niedernhofer

et al. 2010

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

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Werner syndrome and Bloom syndrome result from defects in the RecQ helicases Werner (WRN) and Bloom (BLM), respectively, and display premature aging phenotypes. Similarly, XFE progeroid syndrome results from defects in the ERCC1-XPF DNA repair endonuclease. To gain insight into the origin of cellular senescence and human aging, we analyzed the dependence of sister chromatid exchange (SCE) frequencies on location [i.e., genomic (G-SCE) vs. telomeric (T-SCE) DNA] in primary human fibroblasts deficient in WRN, BLM, or ERCC1-XPF. Consistent with our other studies, we found evidence of elevated T-SCE in telomerase-negative but not telomerase-positive backgrounds. In telomerase-negative WRN-deficient cells, T-SCE—but not G-SCE—frequencies were significantly increased compared with controls. In contrast, SCE frequencies were significantly elevated in BLM-deficient cells irrespective of genome location. In ERCC1-XPF-deficient cells, neither T- nor G-SCE frequencies differed from controls. A theoretical model was developed that allowed an in silico investigation into the cellular consequences of increased T-SCE frequency. The model predicts that in cells with increased T-SCE, the onset of replicative senescence is dramatically accelerated even though the average rate of telomere loss has not changed. Premature cellular senescence may act as a powerful tumor-suppressor mechanism in telomerase-deficient cells with mutations that cause T-SCE levels to rise. Furthermore, T-SCE-driven premature cellular senescence may be a factor contributing to accelerated aging in Werner and Bloom syndromes, but not XFE progeroid syndrome.

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“…Operationally, SCE are reciprocal exchanges of fluorescent intensities between sister chromatids observed in metaphase cells that have replicated twice in the presence of bromodeoxyuridine. Analysis of SCE has been shown to be a sensitive and reproducible indicator for detecting DNA damage induced by chemical mutagens and carcinogens (4)(5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

In utero analysis of sister chromatid exchange: alterations in suscptibility to mutagenic damage as a function of fetal cell type and gestational age.

Kram¹,

Bynum²,

Senula³

et al. 1980

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

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Frequencies of baseline and cyclophosphamide-induced sister chromatid exchanges (SCE) were measured in mouse maternal and fetal cells between days 11 and 19 of gestation. Baseline levels of SCE did not vary as a function of gestational age in either the mother or fetus. Cyclophosphamide-induced SCE frequencies remained constant in maternal cells but declined dramatically in the fetus throughout the latter half of development. Because cyclophosphamide is a metabolically activated mutagen, a direct-acting drug, mitomycin C, was given on days 11 and 15 to determine if the decline in induced SCE levels seen with gestational results from alterations in activating enzymes. A similar decline in mitomycin C-induced SCE levels was noted in fetal tissues as a function of gestational age. Dose-response curves to cyclophosphamide performed on day 13 of gestation showed increases in SCE as a function of cyclophosphamide concentration in both the mother and the fetus. When mutagen-induced SCE levels were compared in different fetal organs, the direct-acting drugs (mitomycin C and daunomycin) were found to induce similar levels in all tissues. Cyclophosphamide, which is metabolically activated, induced higher SCE levels in fetal liver than in lung or gut. Whereas cyclophosphamide induced similar SCE levels in fetal and maternal cells on day 13 of gestation, daunomycin produced fetal SCE levels that were approximately 50% of maternal levels. Simultaneous measurement of the distribution of [14C]cyclophosphamide and [3H]daunomycin in maternal and fetal cells revealed that the lower SCE induction by daunomycin was probably due to decreased ability to cross the placental barrier.

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In vivo sister-chromatid exchange: A sensitive measure of DNA damage

Cited by 122 publications

References 29 publications

A comparison of sister chromatid exchange frequencies in peripheral lymphocytes and bone marrow cells of Fischer 344 and Sprague-Dawley rats

A comparison of sister chromatid exchange frequencies in peripheral lymphocytes and bone marrow cells of Fischer 344 and Sprague-Dawley rats

Hyper telomere recombination accelerates replicative senescence and may promote premature aging

In utero analysis of sister chromatid exchange: alterations in suscptibility to mutagenic damage as a function of fetal cell type and gestational age.

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