Showing papers on "Sister chromatid exchange published in 2007"
TL;DR: A historical perspective of studies spearheaded by Dr. Anthony V. Carrano and colleagues focusing on SCE as a genetic outcome, and the role of the single-strand break DNA repair protein XRCC1 in suppressing SCE is presented.
Abstract: Sister-chromatid exchange (SCE) is the process whereby, during DNA replication, two sister chromatids break and rejoin with one another, physically exchanging regions of the parental strands in the duplicated chromosomes. This process is considered to be conservative and error-free, since no information is generally altered during reciprocal interchange by homologous recombination. Upon the advent of non-radiolabel detection methods for SCE, such events were used as genetic indicators for potential genotoxins/mutagens in laboratory toxicology tests, since, as we now know, most forms of DNA damage induce chromatid exchange upon replication fork collapse. Much of our present understanding of the mechanisms of SCE stems from studies involving nonhuman vertebrate cell lines that are defective in processes of DNA repair and/or recombination. In this article, we present a historical perspective of studies spearheaded by Dr. Anthony V. Carrano and colleagues focusing on SCE as a genetic outcome, and the role of the single-strand break DNA repair protein XRCC1 in suppressing SCE. A more general overview of the cellular processes and key protein "effectors" that regulate the manifestation of SCE is also presented.
253 citations
TL;DR: Data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits in Cornelia de Lange (CdLS).
Abstract: The sister chromatid cohesion apparatus mediates physical pairing of duplicated chromosomes. This pairing is essential for appropriate distribution of chromosomes into the daughter cells upon cell division. Recent evidence shows that the cohesion apparatus, which is a significant structural component of chromosomes during interphase, also affects gene expression and development. The Cornelia de Lange (CdLS) and Roberts/SC phocomelia (RBS/SC) genetic syndromes in humans are caused by mutations affecting components of the cohesion apparatus. Studies in Drosophila suggest that effects on gene expression are most likely responsible for developmental alterations in CdLS. Effects on chromatid cohesion are apparent in RBS/SC syndrome, but data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits.
154 citations
TL;DR: Based on the marked reduction in Holliday junction (HJ) resolution activity in Rad51c-null mouse embryonic fibroblasts, it is proposed that this late function may be associated with HJ resolution.
Abstract: RAD51C is a member of the RecA/RAD51 protein family, which is known to play an important role in DNA repair by homologous recombination. In mice, it is essential for viability. Therefore, we have generated a hypomorphic allele of Rad51c in addition to a null allele. A subset of mice expressing the hypomorphic allele is infertile. This infertility is caused by sexually dimorphic defects in meiotic recombination, revealing its two distinct functions. Spermatocytes undergo a developmental arrest during the early stages of meiotic prophase I, providing evidence for the role of RAD51C in early stages of RAD51-mediated recombination. In contrast, oocytes can progress normally to metaphase I after superovulation but display precocious separation of sister chromatids, aneuploidy, and broken chromosomes at metaphase II. These defects suggest a possible late role of RAD51C in meiotic recombination. Based on the marked reduction in Holliday junction (HJ) resolution activity in Rad51c-null mouse embryonic fibroblasts, we propose that this late function may be associated with HJ resolution.
127 citations
TL;DR: In this paper, a study of possible genetic damage in the people living in regions contaminated with complex mixture of pesticides in Goksu Delta was described, which used methods were chromosomal aberration (CA), sister chromatid exchange analysis (SCE) in peripheral blood lymphocytes, and micronucleus (MN) assay in the buccal epithelial cells.
88 citations
TL;DR: Telomeres and subtelomeres are significantly enriched for SCEs, exhibiting rates of SCE per basepair that are at least 1,600 and 160 times greater, respectively, than elsewhere in the genome.
Abstract: Chromosome ends are known hotspots of meiotic recombination and double-strand breaks. We monitored mitotic sister chromatid exchange (SCE) in telomeres and subtelomeres and found that 17% of all SCE occurs in the terminal 0.1% of the chromosome. Telomeres and subtelomeres are significantly enriched for SCEs, exhibiting rates of SCE per basepair that are at least 1,600 and 160 times greater, respectively, than elsewhere in the genome.
73 citations
TL;DR: In vitro potassium bromate induced CA as much as the positive control, mitomycin-C (MMC), and decreased both the cell proliferation index (PI) and the mitotic index (MI), which provide important evidence about genotoxicity of potassiumbromate on a human cell culture system.
Abstract: The aim of this study was to investigate the genotoxic effects of potassium bromate, which is used as a bleaching agent in flour, on human peripheral blood lymphocytes in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronucleus (MN) tests, and also to determine whether it has any genotoxic potential for humans. Cells were treated with 400, 450, 500, 550 microg/ml concentrations of potassium bromate for 24 and 48 h. The SCE frequencies showed an increase after both treatment periods, however, the differences between the treated cells and the control groups were found to be statistically significant only for the 48-h treatment. In addition, potassium bromate statistically significantly induced CA after the 24-h and 48-h treatment periods. Strikingly, potassium bromate induced CA as much as the positive control, mitomycin-C (MMC). Furthermore, potassium bromate decreased both the cell proliferation index (PI) and the mitotic index (MI). Although micronucleus formation was induced by potassium bromate during the 24-h treatment period in a dose-dependent manner, only the doses 500 and 550 microg/ml yielded statistically significant results. In contrast, MN formation was significantly induced at all doses during the 48-h treatment period. These in vitro results provide important evidence about genotoxicity of potassium bromate on a human cell culture system.
68 citations
TL;DR: It is proposed that RFC(Ctf18) and the Swi1-Swi3 complex function in separate and redundant pathways essential for replication fork stabilization to facilitate sister chromatid cohesion in fission yeast.
Abstract: Sister chromatid cohesion is established during S phase near the replication fork. However, how DNA replication is coordinated with chromosomal cohesion pathway is largely unknown. Here, we report ...
65 citations
TL;DR: It is suggested that Sulfolobus chromosomes have a significant period of postreplicative sister chromatid synapsis, a situation that is more reminiscent of eukaryotic than bacterial chromosome segregation mechanisms.
Abstract: Although the Archaea exhibit an intriguing combination of bacterial- and eukaryotic-like features, it is not known how these prokaryotic cells segregate their chromosomes before the process of cell division. In the course of our analysis of the third replication origin in the archaeon Sulfolobus solfataricus, we identify and characterise sister chromatid junctions in this prokaryote. This pairing appears to be mediated by hemicatenane-like structures, and we provide evidence that these junctions persist in both replicating and postreplicative cells. These data, in conjunction with fluorescent in situ hybridisation analyses, suggest that Sulfolobus chromosomes have a significant period of postreplicative sister chromatid synapsis, a situation that is more reminiscent of eukaryotic than bacterial chromosome segregation mechanisms.
55 citations
TL;DR: Three repeated treatments with genotoxic concentrations of FA with a 3-h interval led to enhanced levels of DPX and MN while the same treatments with a 24-h intervals did not enhance FA genotoxicity but suggested adaptive protection against the DNA-damaging action of FA.
Abstract: Formaldehyde (FA) is known to be genotoxic and mutagenic in proliferating mammalian cells in vitro. The present study was performed to further characterize its genotoxic potential in the V79 Chinese hamster cell line. The induction of DNA strand breaks and DNA-protein cross-links (DPXs) was measured by the comet assay in relationship to the induction of sister chromatid exchanges (SCEs) and micronuclei (MN). Induction of DNA strand breaks was found neither with the standard protocol of the alkaline comet assay nor with modifications using extended electrophoresis times or proteinase K. The concentration-effect relationship for the genotoxic effects was characterized by fitting different curves to the data. A two-phase regression model fitted best in comparison with a linear or a quadratic model and indicated practical thresholds for the induction of SCE and MN. For the induction of DPX as measured by the comet assay, neither a linear concentration-response relationship nor any of the tested models fitted well to the data. Three repeated treatments with genotoxic concentrations of FA with a 3-h interval led to enhanced levels of DPX and MN while the same treatments with a 24-h interval did not enhance FA genotoxicity but suggested adaptive protection against the DNA-damaging action of FA.
53 citations
TL;DR: The disruption of the FBH1 gene in DT40 cells is reported to suggest that Fbh1 acts in parallel with Bloom helicase to control recombination-mediated double-strand-break repair at replication blocks and to reduce the frequency of crossover.
Abstract: Fbh1 (F-box DNA helicase 1) orthologues are conserved from Schizosaccharomyces pombe to chickens and humans. Here, we report the disruption of the FBH1 gene in DT40 cells. Although the yeast fbh1 mutant shows an increase in sensitivity to DNA damaging agents, FBH1(-)(/)(-) DT40 clones show no prominent sensitivity, suggesting that the loss of FBH1 might be compensated by other genes. However, FBH1(-)(/)(-) cells exhibit increases in both sister chromatid exchange and the formation of radial structures between homologous chromosomes without showing a defect in homologous recombination. This phenotype is reminiscent of BLM(-)(/)(-) cells and suggests that Fbh1 may be involved in preventing extensive strand exchange during homologous recombination. In addition, disruption of RAD54, a major homologous recombination factor in FBH1(-)(/)(-) cells, results in a marked increase in chromosome-type breaks (breaks on both sister chromatids at the same place) following replication fork arrest. Further, FBH1BLM cells showed additive increases in both sister chromatid exchange and the formation of radial chromosomes. These data suggest that Fbh1 acts in parallel with Bloom helicase to control recombination-mediated double-strand-break repair at replication blocks and to reduce the frequency of crossover.
47 citations
TL;DR: Findings provide the first genetic evidence that a specific H1 variant plays a unique and important role in the DNA damage response in vertebrates.
TL;DR: Results of the present study suggest that selenite is genotoxicity to V. faba root cells and may be a genotoxic risk to human health.
Abstract: Selenium (Se) is an important metalloid with industrial, environmental, biological and toxicological significance. Excessive selenium in soil and water may contribute to environmental selenium pollution, and affect plant growth and human health. By using Vicia faba micronucleus (MN) and sister chromatid exchange (SCE) tests, possible genotoxicity of sodium selenite and sodium biselenite was evaluated in this study. The results showed that sodium selenite, at concentrations from 0.01 to 10.0 mg/L, induced a 1.9–3.9-fold increase in MN frequency and a 1.5–1.6-fold increase in SCE frequency, with a statistically significantly difference from the control ( P V. faba root cells and may be a genotoxic risk to human health.
TL;DR: It is suggested that interstrand cross links are primary biologically relevant DNA lesions induced by AA for induction of CAs and that cells deficient in HRR were most sensitive followed by Fanconi anaemia like (KO40) suggesting these pathways, especially HRR is very important for the repair of AA-induced lesions.
Abstract: Induction of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) by acetaldehyde (AA) was evaluated in parental and different DNA repair-deficient Chinese hamster ovary (CHO) cell lines to elucidate the mechanisms involved in the protection against AA-induced chromosome damage. Cell lines employed included the parental (AA8), nucleotide excision repair (UV4, UV5, UV61), base excision repair (EM9), homologous recombination repair (HRR) (irs1SF, 51D1)-deficient and Fanconi-like (KO40) ones. The ranking of different cell lines for sensitivity to induction of CAs by AA was 51D1 > irs1SF > KO40 > UV4 > V33-EM9-AA8 > UV61-UV5 in a descending order. Cells deficient in HRR were most sensitive followed by Fanconi anaemia like (KO40) suggesting these pathways, especially HRR is very important for the repair of AA-induced lesions. These observations also suggest that interstrand cross links are primary biologically relevant DNA lesions induced by AA for induction of CAs. Only marginal differences were found between the cell lines for induction of SCEs. The possible mechanisms involved in AA-induced chromosomal alterations are discussed.
TL;DR: XRCC1 siRNA transfection led to an ∼40% decrease in the survival of BRCA2‐deficient cells, supporting a model whereby the accumulation of unrepaired SSBs leads to the accumulationof cytotoxic DNA double strand breaks following replication fork collapse in cells defective in homologous recombination.
Abstract: Previous studies using rodent cells indicate that a deficiency in XRCC1 results in reduced single-strand break repair, increased sensitivity to DNA-damaging agents, and elevated levels of sister chromatid exchange (SCE). Epidemiological studies have suggested an association of certain human XRCC1 polymorphisms with genetic instability and cancer susceptibility. However, investigations on the molecular functions of XRCC1 in human cells are limited. To determine the contributions of this nonenzymatic scaffold protein, we suppressed XRCC1 levels in several human cell lines using small interfering RNA (siRNA) technology. We report that XRCC1 down-regulation in HeLa cells leads to a concomitant decrease in the DNA ligase 3 protein level and an impaired nick ligation capacity. In addition, depletion of XRCC1 resulted in a significantly increased sensitivity to the alkylating agent methyl methanesulfonate and the thymidine base analog 5-hydroxymethyl-2'-deoxyuridine, a slightly increased sensitivity to ethyl methanesulfonate and 1,3-bis(2-chloroethyl)-1-nitrosourea, and no change in the response to camptothecin. We also discovered that a 70-80% reduction in XRCC1 protein leads to an elevated level of SCE in both HeLa cells and normal human fibroblasts, but does not affect chromosome aberrations in the diploid fibroblasts. Last, XRCC1 siRNA transfection led to an approximately 40% decrease in the survival of BRCA2-deficient cells, supporting a model whereby the accumulation of unrepaired SSBs leads to the accumulation of cytotoxic DNA double strand breaks following replication fork collapse in cells defective in homologous recombination.
TL;DR: The results demonstrated that the presence of erythrocytes in the culture system modulated the DNA and cellular damage inflicted by 2, 4‐D and 2,4‐D DMA into human lymphocytes in vitro as well as both 1,4-D and 1,3‐D were more potent genotoxic agents in the presenceof human red cells.
TL;DR: Chronic enzootic haematuria in cattle, aged from 7 to 12 years and pastured in the south of Italy, was cytogenetically investigated for the first time in search of both chromosomal aberrations and sister chromatid exchanges (SCEs).
Abstract: Chronic enzootic haematuria (CEH) is a severe syndrome due to prolonged ingestion of toxic principles of bracken fern, such as quercetin and ptaquiloside. Little information is available on chromosomal instability of cattle with access to bracken fern and suffering from CEH. In the present study, 45 cattle, aged from 7 to 12 years and pastured in the south of Italy, were cytogenetically investigated for the first time in search of both chromosomal aberrations (aneuploidy, gaps, chromatid breaks, chromosome breaks and fragments) and sister chromatid exchanges (SCEs). Of these animals, 30 (group 1) had access to bracken fern and showed signs of CEH, and 15 (group 2; control) did not. Percentage of abnormal cells (aneuploidy, chromatid breaks, chromosome breaks and fragments) was higher in animals affected by CEH (34.7%, group 1) than that (24.3%) reached in the control (group 2). The same results were achieved when including gaps. Indeed, the mean number of cells with structural aberrations excluding gaps (chromatid breaks, chromosome breaks and fragments) per cell was higher (P < 0.001) in animals affected by CEH (0.16 ± 0.36) than that (0.09 ± 0.29) found in the control. Chromosome fragility in cells of animals affected by CEH was also confirmed when applying the SCE test: statistically higher levels (P < 0.001) of SCEs were observed in animals with CEH (7.35 ± 3.59 SCE/cell, group 1) than those in the control (5.40 ± 2.68 SCE/cell).
TL;DR: The results obtained on a single donor may contribute to the understanding of irinotecan toxicity, but further in vitro and in vivo studies are essential in order to clarify remaining issues, especially on possible inter-individual variability in genotoxic responses to the drug.
Abstract: Toxic effects of the antineoplastic drug irinotecan on human blood cells at concentrations of 9.0 microg/ml and 4.6 microg/ml were evaluated in vitro. Using the alkaline and neutral comet assay significantly increased levels of primary DNA damage in lymphocytes were detected. The induction of apoptosis/necrosis, as determined by a fluorescent assay, was also notably increased. Cytogenetic outcomes of the treatment were assessed by the analysis of structural chromosome aberrations and fluorescence in situ hybridization. A significantly higher incidence of chromatid breaks and complex quadriradials was observed. Painted chromosomes 1, 2 and 4 were equally involved in translocations, but only the chromosome 1 was involved in the formation of quadriradials. Sister chromatid exchange analysis was performed in parallel with the analysis of lymphocyte proliferation kinetics. The higher concentration of irinotecan caused almost seven-time increase, while the lower one caused a five-time increase of the basal sister chromatid exchange frequency, accompanied with significant lowering of the lymphocyte proliferation index. Using the cytokinesis-block micronucleus assay, a dose-dependent increase in micronucleus frequency along with the formation of nuclear buds and nucleoplasmic bridges was noticed. Inhibitory effects of irinotecan on enzyme acetylcholinesterase (AChE) were studied in erythrocytes. An IC(50) value of 5.0 x 10(-7) was established. Irinotecan was found to be strong inhibitor of the acetylcholine hydrolysis and to cause a continuous decrease of catalytic activity of AChE. The results obtained on a single donor may contribute to the understanding of irinotecan toxicity, but further in vitro and in vivo studies are essential in order to clarify remaining issues, especially on possible inter-individual variability in genotoxic responses to the drug.
TL;DR: The results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.
TL;DR: The results indicate that DEB damage is persistent in G(0) cells, and DEB is a much more potent genotoxicant than EB, and the carcinogenic effect of butadiene will most likely depend on the degree to whichDEB is produced and reaches target tissues, and to a lesser extent on the ability of EB to reach actively dividing or repair deficient cells.
TL;DR: It is found that XRCC3 activity generates substrates that cause the elevated SCE in blm cells and that BLM with DNA topoisomerase IIIα suppresses the formation of SCE, indicating that BLM acts downstream of XR CC3.
Abstract: Bloom's syndrome (BS), which is caused by mutations in the BLM gene, is characterized by a predisposition to a wide variety of cancers. BS cells exhibit elevated frequencies of sister chromatid exchanges (SCEs), interchanges between homologous chromosomes (mitotic chiasmata), and sensitivity to several DNA-damaging agents. To address the mechanism that confers these phenotypes in BS cells, we characterize a series of double and triple mutants with mutations in BLM and in other genes involved in repair pathways. We found that XRCC3 activity generates substrates that cause the elevated SCE in blm cells and that BLM with DNA topoisomerase IIIα suppresses the formation of SCE. In addition, XRCC3 activity also generates the ultraviolet (UV)- and methyl methanesulfonate (MMS)–induced mitotic chiasmata. Moreover, disruption of XRCC3 suppresses MMS and UV sensitivity and the MMS- and UV-induced chromosomal aberrations of blm cells, indicating that BLM acts downstream of XRCC3.
TL;DR: Segregation analysis of PHOX2B in 13 de novo families with CCHS found that 6 families were informative regarding a parental origin of polyalanine expansion, with all 6 mutants being of paternal origin.
Abstract: The expansion of polyalanine repeats is known to cause at least nine disorders, including congenital central hypoventilation syndrome (CCHS). Unequal crossover has been speculated as the expanding mechanism, in contrast to strand slippage in polyglutamine expansion disorders. We carried out segregation analysis of PHOX2B in 13 de novo families with CCHS and found that 6 families were informative regarding a parental origin of polyalanine expansion, with all 6 mutants being of paternal origin. Four of them were also informative regarding a chromosomal event and their mutants were derived from unequal sister chromatid exchange. It is probable that de novo expansion of polyalanine repeats in CCHS results mainly from unequal sister chromatid exchange during spermatogenesis due to the secondary DNA structure of imperfect trinucleotide repeats encoding polyalanine tracts.
TL;DR: It is shown for the first time that Kombucha from different substrates induced different effects on mitomycin C-treated and -untreated peripheral blood lymphocytes, as well as effects of substrates alone.
Abstract: SUMMARY Kombucha is a refreshing beverage obtained by the fermentation of sweetened black tea with a "tea fungus" (symbiotic cul- ture of acetic acid bacteria and yeasts). It is consumed due to its potential beneficial effects on human health. The aim of this study was to investigate activity of Kombucha on human peripheral blood lymphocytes in vitro. We analyzed Kombucha made from different substrates: Camellia sinensis and Satureja montana, and effects of substrates alone. The frequencies of sister chromatid exchange (SCE) and micronuclei (MN) were scored as genetic endpoints and mitomycin C was used as model mutagen. Kombucha from Camellia sinensis and Camellia sinensis substrate increased frequency of MN and SCE on mitomycin C-treated and -untreated peripheral blood lymphocytes. However, Kombucha from Satureja montana reduced incidence of MN on mitomycin C-treated and -untreated peripheral blood lymphocytes, while SCE frequency was higher than control value. In our pilot study we showed for the first time that Kombucha from different substrates induced different effects on mitomycin C-treated and -untreated peripheral blood lymphocytes.
TL;DR: The present results suggested the potent antigenotoxic effects of xanthones in mangosteen, which is widely used as health food because of its many pharmacological properties.
Abstract: The inhibitory effects of xanthone on genotoxicity induced by paraquat and NaNO2 in cultured Chinese hamster lung (CHL) cells were examined. Xanthone forms the central core of xanthones. Xanthones are present in mangosteen, which is widely used as health food because of its many pharmacological properties. Paraquat (PQ, a superoxide anion generator) and NaNO2 induce genotoxic effects, including sister chromatid exchange (SCE) and decreased cell cycle rate, in CHL cells. Xanthone inhibited the genotoxic effects of PQ and NaNO2 at concentrations of more than 5 μM. The present results suggested the potent antigenotoxic effects of xanthones in mangosteens.
TL;DR: DNA crosslinking at the replication fork is proposed as a model which could explain the mechanistic link between ELF EMF exposure and increased SCE frequency.
Abstract: The in vitro cytomolecular technique, sister chromatid exchange (SCE), was applied to test the clastogenic potentiality of extremely low frequency (ELF) electromagnetic fields (EMFs) on human peripheral blood lymphocytes (HPBLs). SCE frequencies were scored in dividing peripheral blood lymphocytes (PBLs) from six healthy male blood donors in two rounds of experiments, R1 and R2, to determine reproducibility. Lymphocyte cultures in the eight experiments conducted in each round were exposed to 50 Hz sinusoidal (continuous or pulsed) or square (continuous or pulsed) MFs at field strengths of 1 microT or 1 mT for 72 h. A significant increase in the number of SCEs/cell in the grouped experimental conditions compared to the controls was observed in both rounds. The highest SCE frequency in R1 was 10.03 for a square continuous field, and 10.39 for a square continuous field was the second highest frequency in R2. DNA crosslinking at the replication fork is proposed as a model which could explain the mechanistic link between ELF EMF exposure and increased SCE frequency.
TL;DR: It is shown that cells lacking RMI1 have a mitotic delay, which is partly dependent on the spindle checkpoint, and are sensitive to the microtubule depolymerizing agent benomyl.
Abstract: The Saccharomyces cerevisiae RecQ-mediated genome instability (Rmi1) protein was recently identified as the third member of the slow growth suppressor 1–DNA topoisomerase III (Sgs1–Top3) complex, which is required for maintaining genomic stability. Here, we show that cells lacking RMI1 have a mitotic delay, which is partly dependent on the spindle checkpoint, and are sensitive to the microtubule depolymerizing agent benomyl. We show that rmi1 and top3 single mutants are defective in sister chromatid cohesion, and that deletion of SGS1 suppresses benomyl sensitivity and the cohesion defect in these mutant cells. Loss of RAD51 also suppresses the cohesion defect of rmi1 mutant cells. These results indicate the existence of a new pathway involving Rad51 and Sgs1-Top3-Rmi1, which leads to the establishment of sister chromatid cohesion.
TL;DR: The relationship between WRN and the post-replication repair protein RAD18 is examined by generating deletion derivatives in chicken DT40 cells to suggest that WRN functions in a pathway involving RAD18 under damage-inducing conditions.
Abstract: Werner syndrome (WS), caused by mutations in a gene (WRN) that encodes a RecQ DNA helicase, is characterized by premature aging and cancer predisposition. Cells derived from WS patients show sensitivity to several DNA damaging agents. Previous studies revealed that the WRN protein plays roles in DNA repair or damage tolerance, although it was not yet assigned to a specific pathway. Here we examined the relationship between WRN and the post-replication repair protein RAD18 by generating deletion derivatives in chicken DT40 cells. The frequency of spontaneous sister chromatid exchange in WRN−/−/RAD18−/− double mutant cells was slightly increased compared to that of either single mutant. However, the sensitivity of WRN−/−/RAD18−/− cells to 4-nitroquinoline 1-oxide and methyl methanesulfonate was almost the same as that of RAD18−/− cells. Moreover, the cisplatin sensitivity of RAD18−/− cells was slightly suppressed by disruption of WRN. These data suggest that WRN functions in a pathway involving RAD18 under damage-inducing conditions.
TL;DR: The present findings indicate that 2,4‐D has a low to moderate genotoxic activity and a slight, not statistically significant proliferative effect at the lowest dose of 0.5 mg/embryo.
Abstract: Before incubation, chick embryos were treated with the herbicide 2,4-dichlorophenoxy acetic acid (2,4-D) by injecting onto the inner shell membrane solutions of 0, 0.5, 1, 2, or 4 mg 2,4-D. A commercial formulation containing 37% 2,4-D iso-octyl ester as active ingredient and pure 2,4-D were tested. Sister chromatid exchange (SCE) and cell cycle kinetics were examined at days 4, 7, and 10 from 22 to 30 embryos per group. After 4 days of exposure to commercial 2,4-D, a small (P < 0.05) dose-related increase of SCE was seen for the 4-mg group. An enhanced SCE response upon long-term exposure to 2,4-D was apparent. After 10 days of exposure, SCE frequencies for the 2- and 4-mg commercial 2,4-D, and 4-mg pure 2,4-D groups were significantly higher than for the controls. A significant slowing of cell cycle at concentrations at and above 1 mg was seen. Also observed was a slight, not statistically significant proliferative effect at the lowest dose of 0.5 mg/embryo. Consistent with the results from other test systems, the present findings indicate that 2,4-D has a low to moderate genotoxic activity.
TL;DR: It can be concluded that benzothiazole derivatives showed mutagenic activity and were also able to exert a genotoxic effect reducing both the replication index and mitotic index.
Abstract: Derivatives of 2-aryl-substitute (o-hydroxy-, m-bromo-, o-methoxy-, o-nitro-phenyl or 4-pyridyl) benzothiazole were synthesized and tested for their mutagenicity in in vitro assays: (i) in the Ames test with Salmonella typhimurium TA98 and TA100 strains; and (ii) in the sister chromatid exchange (SCE) in cultured human lymphocytes. The four of compounds (BT-11, B-12, BT-14 and BT-15) caused statistically significant increase in revertant colonies of TA98 and TA100. Treatment of lymphocytes with compounds also caused a significant increase in SCE/cell in association with high levels and long exposure (300 µg/mL and 48 h) of the four compounds. It can be concluded that benzothiazole derivatives showed mutagenic activity and were also able to exert a genotoxic effect reducing both the replication index and mitotic index.
TL;DR: An 18-year old girl who presented with short stature was diagnosed with Bloom syndrome based on an extremely increased frequency of sister chromatid exchanges, and mild lens opacities bilaterally were revealed.
Abstract: Bloom syndrome is an autosomal recessive disorder characterized by proportionate short stature, photosensitivity, immunodeficiency, hypogonadism and a tendency to develop various malignancies. The greatly increased frequency of sister chromatid exchanges (reciprocal exchange of homologous segments between the two sister chromatids of a chromosome) is regarded as pathognomonic for BS. We describe an 18-year old girl who presented with short stature. She was diagnosed with BS based on an extremely increased frequency of sister chromatid exchanges. Ophthalmological examination revealed mild lens opacities bilaterally, which, to our knowledge, has not been previously reported to be associated with BS.
TL;DR: It was found to be dose dependant and the period dependancy showed a decline after 24 hr, and there was significant induction of SCEs in both single and multiple dose series with both the compounds.
Abstract: Genotoxicity of furfuryl alcohol and 2-furyl methyl ketone is evaluated by sister chromatid exchange analysis (SCEs) in mouse bone marrow system using standard technique. Three doses of the compounds ranging from 1000-4000 ppm were given by oral gauvage to experimental animals for one day in single dose series and for five consecutive days in multiple dose series to simulate a human situation. 5-Bromodeoxyuridine (5-Brdu) was intraperitoneally injected at hourly intervals for 6 hr at a concentration of 0.04mg/g body weight. In both single and multiple dose series the animals were exposed to 5-Brdu for 26 hr and were sacrificed after 12, 24 and 48 hr following last feeding. Control animals received distilled water and same concentration of Brdu. Bone marrow slides were prepared and stained as per standard procedure. 100 metaphase spreads in second mitotic division were scored from each dose and period and subjected to statistical analysis. There was significant induction of SCEs in both single and multiple dose series with both the compounds. It was found to be dose dependant and the period dependancy showed a decline after 24 hr.