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Sister chromatid exchange

About: Sister chromatid exchange is a research topic. Over the lifetime, 3187 publications have been published within this topic receiving 90029 citations. The topic is also known as: replication-born DSB repair by SCE & GO:1990414.


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Journal ArticleDOI
TL;DR: It is shown that constitutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (iHR), a precedent for CN-LOH, and therapeutic reduction of ROS may thus prevent leukemic progression and relapse in myeloid malignancies.
Abstract: Acquired copy neutral LOH (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here, we show that constitutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F-mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared with wild-type FLT3 NK-AML. HR was harmonized to S phase of the cell cycle to repair broken chromatids and prevent iHR. Increased HR activity in G0 arrested primary FLT3-ITD NK-AML in contrast to wild-type FLT3 NK-AML. Cells expressing mutated FLT3-ITD demonstrated a relative increase in mutation frequency as detected by thymidine kinase (TK) gene mutation assay. Moreover, resistance was associated with CN-LOH at the TK locus. Treatment of FLT3-ITD- and JAK2V617F-mutant cells with the antioxidant N-acetylcysteine diminished reactive oxygen species (ROS), restoring iHR and HR levels. Our findings show that mutated FLT3-ITD and JAK2 augment ROS production and HR, shifting the cellular milieu toward illegitimate recombination events such as iHR and CN-LOH. Therapeutic reduction of ROS may thus prevent leukemic progression and relapse in myeloid malignancies. Cancer Res; 77(7); 1697-708. ©2017 AACR.

25 citations

Journal ArticleDOI
TL;DR: Samples of alcohol and alcoholic beverages induced SCEs in Chinese hamster ovary cells in the presence of rat-liver homogenate for metabolic activation and SCE tests with acetaldehyde indicate that SCE induction by alcohol is caused by formation of acetaldehyde.
Abstract: Samples of alcohol and alcoholic beverages induced SCEs in Chinese hamster ovary cells in the presence of rat-liver homogenate for metabolic activation SCE tests with acetaldehyde, and measurement of acetaldehyde concentration in tests with alcohol, indicate that SCE induction by alcohol is caused by formation of acetaldehyde

25 citations

Journal ArticleDOI
TL;DR: Comparison of the DNA alkylation products produced by CNU and ENU treatment of 9L cells suggests that the formation of the intrastrand crosslink N7-bis(guanyl)ethane and the interstrand crosslink 1-(3- deoxycytidyl)-2-(1-deoxyguanosinyl)ethanes by CNu is responsible for the increased effectiveness of CNU treatment at both induction of SCEs and cytotoxicity.
Abstract: The induction of sister-chromatid exchanges (SCEs) and cytotoxicity in 9L cells treated with monofunctional and bifunctional alkylating agents has been investigated. Three classes of monofunctional and bifunctional agents were studied: nitrosoureas, mustards and epoxides. Independent of class the bifunctional agents were 55–630-fold more effective at inducing SCEs and 300–2400-fold more effective at inducing cellular cytotoxicity than the corresponding monofunctional agents. Comparing the induction of SCEs and cytotoxicity by these agents showed that these two cellular responses to DNA damage are highly correlated. The extent of DNA alkylation in cells treated with 1-ethyl-1-nitrosourea (ENU) or 1-(2-chloro-ethyl)-1-nitrosourea (CNU) was similar indicating that the increased effectiveness of CNU to induce SCEs and cytotoxicity was not due to increased DNA alkylation. Molecular dosimetry calculations indicate that for CNU and ENU treatment of 9L cells there are 116 and 8500 alkylations per SCE induced and 2.6 × 10 4 and 4.6 × 10 6 alkylations at the dose required to reduce survival of 9L cells by 90%. Comparison of the DNA alkylation products produced by CNU and ENU treatment of 9L cells suggests that the formation of the intrastrand crosslink N 7 -bis(guanyl)ethane the interstrand crosslink 1-(3-deoxycytidyl)-2-(1-deoxyguanosinyl)ethane by CNU is responsible for the increased effectiveness of CNU treatment at both induction of SCEs and cytotoxicity.

25 citations

Journal ArticleDOI
TL;DR: CsA has SCE inducibility and the data suggest that CsA has a mutagenic effect on human lymphocytes, which is in line with previous reports on cyclosporine and SCE.
Abstract: To examine whether cyclosporine (CsA) has mutagenic potential against human cells, we analyzed sister chromatid exchange (SCE) induction by CsA using human lymphocytes in vitro. SCE frequencies increased significantly in the lymphocytes treated with 1 microgram/ml and 5 micrograms/ml CsA, though the frequencies seemed to be less than one hundredth of those induced by mitomycin C (MMC). The value of induced SCE depended on CsA concentration. This result indicates that CsA has SCE inducibility. The data also suggest that CsA has a mutagenic effect on human lymphocytes.

25 citations

Journal ArticleDOI
TL;DR: The sister chromatid exchange frequency in bone‐marrow cells of 12 untreated patients with chronic myelocytic leukemia was analysed and the differences found were unrelated to patients' age and contraction state of the chromosomes.
Abstract: The sister chromatid exchange (SCE) frequency in bone-marrow cells of 12 untreated patients with chronic myelocytic leukemia (CML) was analysed and compared with the SCE frequency in bone-marrow cells of nine healthy persons. In normal persons the SCE ranged from 3.64 to 5.15 per cell. In CML patients the SCE was significantly lower, ranging from 2.32 to 3.44 per cell. The differences found were unrelated to patients' age and contraction state of the chromosomes. It is suggested that the leukemic process could account for the low SCE rate.

25 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20238
202222
20215
202011
201914
201811