Showing papers on "Sister chromatid exchange published in 1994"
Journal Article•
TL;DR: An increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk in peripheral blood lymphocytes, according to an ongoing Nordic cohort study of cancer incidence.
Abstract: Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange or micronuclei in PBL. In order to standardize for the interlaboratory variation, the results were trichotomized for each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). In this second follow-up, a total of 85 cancers were diagnosed during the observation period (1970-1991). There was no significant trend in the standardized incidence ratio with the frequencies of sister chromatid exchange or micronuclei, but the data for these parameters are still too limited to allow firm conclusions. There was a statistically significant linear trend (P = 0.0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk.
510 citations
TL;DR: The distribution of DNA migration among cells, a function of dose, revealed that the majority of exposed cells expressed more DNA damage than cells from control cultures and that with increasing length ofDNA migration the variability in migration among Cells increased as well.
Abstract: Sodium arsenite (NaAsO2) and cadmium sulphate (CdSO4) were tested for their ability to induce genotoxic effects in the single cell gel (SCG) assay and the sister chromatid exchange (SCE) test in human blood cultures in vitro Both metals induced DNA damage in white blood cells that was expressed and detected as DNA migration in the SCG assay Dose dependent effects were seen for cadmium in concentrations from 5 × 10−4-5 × 10−3 M and for arsenic in concentrations from 2 × 10−4-15 × 10−3 M The distribution of DNA migration among cells, a function of dose, revealed that the majority of exposed cells expressed more DNA damage than cells from control cultures and that with increasing length of DNA migration the variability in migration among cells increased as well
Treatment of cells for 2 hr or 24 hr beginning 48 hr after the start of the blood cultures did not increase the SCE frequency in the case of cadmium but caused a small but significant SCE induction with arsenic at the highest concentration The metal concentrations which could be investigated in the SCE test were much lower due to a strong toxic effect Metal concentrations which were toxic in the SCE test were without visible effect in the SCG assay Thus the two endpoints for the determination of genotoxic effects in vitro differed markedly with respect to the detection of genotoxicity induced by metals These differences and the biological significance of the findings are discussed © 1994 Wiley-Liss, Inc
150 citations
TL;DR: The results reported in this work show that quercetin can produce the OH.
Abstract: Quercetin has been the subject of numerous studies on its genetic toxicity and carcinogenicity. Despite its well-proven genetic damaging activity for various genetic end-points (reverse mutations, induction of SOS functions, induction of sister chromatid exchanges, chromosomal aberrations and micronuclei), the mechanisms of genetic damage by quercetin remain, by and large, unknown. The present study aims to further extend the observations on the possible active oxygen species mediated DNA-damaging activity of quercetin and the role of cytochrome P450-dependent metabolism on the genotoxicity of quercetin. The results reported in this work show that quercetin can produce the OH. radical, as assessed by deoxyribose degradation in the presence of Fe3+/EDTA (ethylenediaminetetraacetic acid), and that it induces strand breakage in isolated plasmidic DNA (pUC18). The data support the hypothesis that the production of OH. is mediated by H2O2. The results with genetically engineered V79 cells expressing rat cytochromes 1A1, 1A2 and 2B1 failed to demonstrate metabolism of quercetin, as indicated by the fact that neither an enhancement nor a decrease in the genotoxicity of quercetin was observed. Results obtained on the pH dependence of the induction of chromosomal aberrations by quercetin in V79 cells show that, as the pH value of the medium is increased to 8.0, there is a significant increase in the number of aberrant cells, as expected if oxygen radicals are responsible for the formation of chromosomal aberrations.
73 citations
TL;DR: O6-Methylguanine (m6G) is an altered base produced in DNA by SN1 methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).
Abstract: O6-Methylguanine (m6G) is an altered base produced in DNA by SN1 methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) This lesion is repaired by the protein O6-methylguanine-DNA methyltransferase (MGMT) in normal human cell lines, but is not repaired in certain human tumor lines that are termed Mex- or Mer- Compared with repair-proficient cell lines, such repair-deficient tumor lines are hypersensitive to the production by MNNG of sister-chromatid exchanges (SCE), mutations and lethality We report here that MNNG treatment produces 1 SCE for every 42 +/- 10 m6G formed in the genome of Mer- tumor cells, 1 6TG-resistant mutant for every 8 (range of 5-14) m6G produced statistically in the coding region of the hypoxanthine phosphoribosyltransferase gene, and 1 lethal event per 6650 +/- 1200 m6G In addition, in vitro base mismatch incision at m6G: BrU pairs was similar to that at m6G: T pairs, the lesions that likely initiate SCE production We conclude that m6G residues in genomic DNA are very recombinogenic as well as highly mutagenic in Mer- human tumor cells The results are interpreted in terms of the relationship between methylation-induced SCE and G: T mismatch recognition
58 citations
TL;DR: The data strongly suggest an impaired checkpoint function in p53‐deficient cells when DNA is damaged, and no difference in UV sensitivity and repair of UV‐induced DNA damage was found among the 3 genotypes.
Abstract: UV-induced sister chromatid exchanges (SCEs) in p53-deficient mouse cells were studied to obtain more evidence regarding the involvement of p53 protein in the DNA repair pathway as a checkpoint protein. After 5 J/m2 UV irradiation, mutant-type homozygous cells for p53-deficiency showed the same number of SCEs as the heterozygous and wild-type homozygous cells. In the heterozygous and wild-type homozygous cells, no further increase of SCEs was observed after 10 J/m2 UV irradiation. In contrast, in mutant-type homozygous cells about twice as many SCEs were induced by 10 J/m2 UV as by 5 J/m2 UV. In mutant-type homozygous cells, fractions of S-phase cells decreased just after 10 J/m2 UV irradiation, but recovered to higher than control levels within a short time, while in heterozygous and wild-type homozygous cells, the decrease in S-phase cells was prolonged by more than 6 hr and no increase above control levels was observed. Although no difference in UV sensitivity and repair of UV-induced DNA damage was found among the 3 genotypes, which were determined by the relative colony-forming ability after UV irradiation and removal of thymine dimers and (6-4) photoproducts from cellular DNA, our data strongly suggest an impaired checkpoint function in p53-deficient cells when DNA is damaged.
56 citations
TL;DR: Genotoxicity of a widely used estrogen, Mestranol, was undertaken using in vitro, in vivo and host-mediated assay with bacteria as indicator organism, and both Ames Salmonella/S9 assay with and without S9 mix showed any significant increase/decrease in the His+ revertants.
Abstract: Genotoxicity of a widely used estrogen, Mestranol, was undertaken using in vitro, in vivo and host-mediated assay with bacteria as indicator organism. Analyses of chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes and chromosome aberrations, micronuclei and sister chromatid exchanges (SCEs) in bone-marrow cells of mice showed the drug to be capable of attacking the genetic material. However, both Ames Salmonella/S9 assay with and without S9 mix and host-mediated assay using same tester strains of Salmonella, did not show any significant increase/decrease in the His+ revertants.
36 citations
TL;DR: In general, MX was more toxic to CHO cells treated in PBS compared with exposure in medium or medium plus 2.5% serum, and the most pronounced genotoxic effect of MX was observed in CAs (100% aberrant cells at the dose level of 4 micrograms/ml, exposure in PBS).
Abstract: The strong bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was tested for the induction of mutation at the Na/K ATPase locus to ouabain resistance (OuaR), sister-chromatid exchanges (SCEs), and chromosome aberrations (CAs) in Chinese hamster ovary (CHO) cells without metabolic activation. MX increased the frequency of OuaR mutants in CHO cells when the cells were treated with it in PBS (effective dose range 2-3 micrograms/ml) or in medium (McCoy's 5A) without serum (effective dose range 20-30 micrograms/ml). MX also induced SCEs in CHO cells, at 0.19-1.5 microgram/ml, exposure in PBS; at 6-24 micrograms/ml, exposure in medium; and at 3-24 micrograms/ml, exposure in medium plus 2.5% fetal calf serum. The maximum induction of SCEs was about 1.5-2.5-fold compared with control level, irrespective of exposure conditions (PBS, medium or medium plus serum). The most pronounced genotoxic effect of MX was observed in CAs (100% aberrant cells at the dose level of 4 micrograms/ml, exposure in PBS) which were mainly of the chromatid type. In general, MX was more toxic to CHO cells treated in PBS compared with exposure in medium or medium plus 2.5% serum.
35 citations
TL;DR: An important prediction of the model is that in non-selective conditions the cells with amplified sequences gradually disappear from the population even if they are not at a growth disadvantage, though rare cells with a very large number of amplified sequences might continue to exist.
35 citations
TL;DR: It is shown that chemicals and environmental agents that produce a variety of DNA lesions, including bulky adduct, thymidine dimers, interstrand cross-links, double-strand breaks alkylated bases, can stimulate recombination to yield reciprocal translocations.
Abstract: DNA-damaging agents can stimulate the formation of directed reciprocal translocations of Saccharomyces cerevisiae containing his3 recombinational substrates to generate chromosomal rearrangements. Such agents were compared with those that can stimulate sister- chromatid recombination. We show that chemicals and environmental agents that produce a variety of DNA lesions, including bulky adduct, thymidine dimers, interstrand cross-links, double-strand breaks and alkylated bases, can stimulate recombination to yield reciprocal translocations. Of the agents teted, only the alkylating agents methyl methanesulfonate (MMS) and N-methyl-N′-nitro-N-nitrosoguinidine (MNNG), and a bifunctional agent that causes bulky DNA adducts, 4-nitroquinoline-N-oxide (4-NQO), significantly stimulate sister-chromatid recombination in our assay. Factors that contribute to the stimulation of interchromosomal recombination include strain genetic background and ploidy.
30 citations
TL;DR: A plot of cytotoxicity versus SCEs indicated a good correlation between these two parameters for topoisomerase II inhibitors and not for mytomicin C, and the plot of DSBs versus S CEs showed a very good correlation.
Abstract: Doxorubicin, ellipticine and etoposide are antineoplastic drugs with topoisomerase II inhibitory activity. The relationship between drug-induced sister-chromatid exchanges (SCEs) or chromosomal aberrations (CAs) and cytotoxicity, or drug-induced DNA double-strand breaks (DSBs) and cytotoxicity, or drug-induced SCEs and DSBs was investigated in human ovarian cancer cells sensitive (A2780) and resistant (A2780-DX3) to topoisomerase II inhibitors. 30-min drug treatments produced SCEs, CAs and DSBs in sensitive cells, doxorubicin being more potent than etoposide at equimolar concentrations. The same treatments of resistant (A2780-DX3) cells did not produce chromosomal damage (SCEs, CAs, DSBs) and no cytotoxicity was observed. A plot of cytotoxicity versus SCEs indicated a good correlation between these two parameters for topoisomerase II inhibitors and not for mytomicin C. The plot of DSBs versus SCEs also showed a very good correlation.
29 citations
TL;DR: Cytogenetic monitoring of a group of traffic policemen from Cairo, Egypt, was an example of a human population study and the increase in chromosome damage among the traffic policemen was enhanced further by smoking.
Abstract: Humans are exposed to a large number of environmental genotoxic agents. These can increase the probability that somatic mutation will occur. The use of genotoxicity testing is essential for assessment of potential human toxicity so that hazards can be prevented. Cytogenetic monitoring of human populations exposed to chemicals has proved to be a useful tool for detecting the chemical mutagenic effects. Cytogenetic analysis of human chromosomes in peripheral lymphocytes allows direct detection of mutation in somatic cells. Cytogenetic monitoring of a group of traffic policemen from Cairo, Egypt, was an example of a human population study. The induction of chromosomal damage was studied in a group of 28 traffic policemen with exposure of over 10 years and a control group of 15 policemen trainers. Blood lead level was significantly higher in the traffic policemen (30 +/- 8.7) unit compared to the control group (18.2 +/- 1.2) unit. The percentage of chromosomal aberrations (7.7 +/- 3.1), as well as the mean sister chromatid exchanges (7.5 +/- 3.4), were significantly higher among the traffic policemen than in the control group. The percentage of chromosomal aberrations was 2.8 +/- 2.1 and the mean sister chromatid exchanges was 4.8 +/- 2.9 in the control group. On the other hand, the increase in chromosome damage among the traffic policemen was enhanced further by smoking. Several problems that are found in biomonitoring studies are discussed.
TL;DR: The significant increase in the frequency of micronucleated cells coupled with the increase inThe frequency of chromosome/ chromatid bridges and lagging chromosomes/chromatids suggest that these two are clastogenic for Vicia faba root cells.
Abstract: The clastogenic property of two lanthanides, Praseodymium and Neodymium, was evaluated by scoring the frequencies of micronucleated cells in the interphase and chromosome/chromatid aberrations at ana-telophases in root tips of Vicia faba L. The significant increase in the frequency of micronucleated cells coupled with the increase in the frequency of chromosome/chromatid bridges and lagging chromosomes/chromatids suggest that these two are clastogenic for Vicia faba root cells.
TL;DR: The results indicate that specific and significant differences in the response to mutagens may exist between 'normal' Chinese hamster cell lines which might be relevant for genotoxicity testing.
TL;DR: A BrdU incorporation period of 48 to 60 h would seem to be most appropriate for the sister chromatid exchange (SCE) tests carried out in gill cells of M. galloprovincialis, whereas the 12 to 24 h exposure would give the best results for replication band analysis.
Abstract: A technique of sister chromatid differentiation (SCD) using bromodeoxyuridine (BrdU) incorporation and a modification of the fluorescence plus Giemsa (FPG) method was employed to determine cell-proliferation kinetics in gill tissue of the mussel Mytilus galloprovincialis. Dose-dependent proliferation inhibition was examined. In vivo administration of BrdU for 12, 24, 36, 48, 60, 72, 84, and 96 h was studied. Our data show that the highest yield of second-generation metaphase plates is obtained after 60 h BrdU treatment; the duration of a cell cycle is 24 to 30 h. On the basis of these data, a BrdU incorporation period of 48 to 60 h would seem to be most appropriate for the sister chromatid exchange (SCE) tests carried out in gill cells of M. galloprovincialis, whereas the 12 to 24 h exposure would give the best results for replication band analysis.
TL;DR: It is indicated that chlorophyllin per se did not have any effect on the SCE frequency and that the dose of 100 micrograms/g bw protects 100% against the induction of SCE by 1.0 Gy of gamma-rays.
Abstract: The aim of the present work is to determine the radioprotective capacity of chlorophyllin, by measuring the reduction of γ-ray-induced sister-chromatid exchange (SCE) in murine bone marrow cells in vivo. The results obtained in two separate experiments, using 10, 50 and 100 μg of chlorophyllin per g of body weight (bw), indicate that chlorophyllin per se did not have any effect on the SCE frequency and that the dose of 100 μg/g bw protects 100% against the induction of SCE by 1.0 Gy of γ-rays; 50 μg/g bw protects less than 50% and 10 μg/g bw affords no protection.
TL;DR: The data suggest that pretreatment with nickel interferes with the repair of radiation-induced DNA damage and potentially cause mistakes in DNA repair, and suggest that nickel-induced abnormal DNA repair may be a mechanism for its carcinogenic properties.
Abstract: Carcinogenic nickel compounds are usually found to be weak mutagens; therefore these compounds may not exert their carcinogenic activity through conventional genotoxic mechanisms. On the other hand, the activities of many nickel compounds have not been adequately investigated. We evaluated the genotoxic activities of nickel acetate using conventional chromosome aberration and sister chromatid exchange assays and found that there was no increase of chromosome aberrations or sister chromatid exchanges, although the highest dose (1000 {mu}M) caused mitotic inhibition. In addition, we investigated its effect on DNA repair using our challenge assay. In this assay, lymphocytes were exposed to 0.1 to 100 {mu}M nickel acetate for 1 hr during the G0 phase of the cell cycle. The cells were washed free of the chemical and, 1.5 hr later, were irradiated with two doses of {gamma}-rays (75 cGy per dose separated by 60 min). A significant dose-dependent increase of chromosome translocations was observed (p<0.05). The increase is more than expected based on additive effects from exposure to nickel or {gamma}-rays individually. In contrast to the increase of chromosome translocations, there was no increase in chromosome deletions, although there was a nickel dose-dependent reduction of mitotic indices. Our data suggest that pretreatment withmore » nickel interferes with the repair of radiation-induced DNA damage and potentially cause mistakes in DNA repair. Furthermore, we suggest that nickel-induced abnormal DNA repair may be a mechanism for its carcinogenic properties. The DNA repair problems that we observed after exposure to low doses of nickel may be viewed as a type of adaptive response. Contrary to some investigators who showed that adaptive responses may be beneficial, our data indicated that some responses may cause more problems than expected. 39 refs., 3 figs.« less
TL;DR: The use of cell lines with defined metabolic capabilities seems to be a valuable tool to study specific metabolic pathways important in the activation of procarcinogens.
Abstract: A genetically engineered V79 cell line expressing rat CYP1A2 and another cell line expressing rat CYP1A2 as well as endogenous acetyltransferase activity, as well as CYP-deficient parental V79 cell lines, were used to assess the genotoxicity of the aromatic amines and amides 2-aminoanthracene, 2-aminofluorene, 2-acetylaminofluorene, 4-acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoline, with chromosomal aberrations and sister chromatid exchanges as the end-points. None of the test compounds showed a clear effect on the frequency of chromosomal aberrations in any cell line used. Sister chromatid exchanges, however, were induced by 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene in the CYP1A2-proficient cells, but not in the CYP1A2-deficient cells. The presence of acetyltransferase activity enhanced the effect of 2-aminoanthracene, 2-aminofluorene and 2-acetylaminofluorene. 4-Acetylaminofluorene and 2-amino-3-methylimidazo[4,5-f]quinoline did not induce sister chromatid exchanges in the investigated cell lines. The use of cell lines with defined metabolic capabilities seems to be a valuable tool to study specific metabolic pathways important in the activation of procarcinogens.
TL;DR: The lack of significant difference in response between the two groups of malnourished children suggests that the effects observed at the cytogenetic level are caused by severe malnutrition per se, and not by any associated infection.
Abstract: The frequency of sister-chromatid exchanges (SCE) and the rate of cell proliferation were evaluated through differential staining of sister chromatids in mitogen-stimulated cultured lymphocytes sampled from five well-nourished children, from seven severely malnourished children infected with bacterium, and from 10 severely malnourished children following treatment for infection with antimicrobial drugs 2 weeks before blood sampling. The replication indices at 48 h of culture were higher in both groups of malnourished children than in the well-nourished children, indicating either a faster response to PHA and/or a shorter cell cycle in lymphocytes of these patients. The average frequency of SCE per mitosis was also significantly higher than in the control group. The mitotic index was similar in the three groups of children. The lack of significant difference in response between the two groups of malnourished children suggests that the effects observed at the cytogenetic level are caused by severe malnutrition per se, and not by any associated infection.
TL;DR: The rate of lymphocyte proliferation kinetics showed an increase after the metronidazole treatment in all patients, indicating a possible immunostimulatory action.
Abstract: Metronidazole, an effective agent for the treatment of protozoan infections, is frequently used in developing countries. However, the employment of this drug has been questioned in view of its mutagenicity in bacteria and carcinogenicity in mice. A genotoxic study was carried out in which cellular proliferation kinetics and the frequency of sister-chromatid exchanges were determined in human peripheral blood lymphocytes from 12 individuals treated with therapeutic doses of metronidazole. No effect was observed on mitotic index with the treatment, although a significant increase was found in three individuals after treatment. No increase of sister-chromatid exchanges was detected. The rate of lymphocyte proliferation kinetics showed an increase after the metronidazole treatment in all patients, indicating a possible immunostimulatory action.
TL;DR: Increasing concentrations of Viscum album L. extracts were shown to significantly reduce sister chromatid exchange (SCE) frequency of phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells of healthy individuals.
TL;DR: This protocol uses phytohemagglutinin‐stimulated cultures of blood lymphocytes as a source of proliferating cells andchromatids with bifilar substitution exhibit a lighter purple stain than their unifilarly substituted sister chromatids.
Abstract: Two requirements for the cytogenetic analysis of sister-chromatid exchanges (SCEs) in somatic cells are (1) a population of actively proliferating cells that will provide an adequate number of metaphases and (2) sister chromatids that in some way are differentially labeled or stained in the metaphases. SCEs can be recognized as abrupt discontinuities in the staining patterns of the two chromatids of a metaphase chromosome at what appear to be identical sites, with reciprocal switching from one chromatid to its sister. This protocol uses phytohemagglutinin (PHA)-stimulated cultures of blood lymphocytes as a source of proliferating cells. The cells are incubated with the thymidine analog BrdU. Slides prepared from fixed cells with BrdU-substituted chromosomes are treated with Hoechst 33258, exposed to light and heat, and then Giemsa-stained to produce differentially stained chromosomes. The chromatids with bifilar substitution exhibit a lighter purple stain than their unifilarly substituted sister chromatids.
TL;DR: The CYP1A1-inducing potency and genotoxicity of the samples were not correlated: in a bacterial DNA repair assay without metabolic activation and in a mammalian sister chromatid exchange test in the presence of metabolic activation the sampleswere virtually non-genotoxic.
Abstract: Cytochrome P450IA1 (CYP1A1) induction of Hepa-1 mouse and H4IIE rat hepatoma cell lines was compared using selected environmental samples. The results were in agreement for both cell lines: no induction was observed for the fly ash extract from peat combustion, an intermediate induction was found for the fly ash extract from biosludge combustion, and a strong induction was detected for natural peat extract. However, Hepa-1 responded to the samples more sensitively than did H4IIE: the half maximal induction (ED50) values for Hepa-1 were smaller than those for H4IIE. In a bacterial DNA repair assay without metabolic activation and in a mammalian sister chromatid exchange test in the presence of metabolic activation the samples were virtually non-genotoxic. Thus the CYP1A1-inducing potency and genotoxicity of the samples were not correlated. In light of these results, the CYP1A1 induction test might be a useful addition to conventional genotoxicity tests, which may fail to detect potentially harmful compounds/mixtures.
Icos1
TL;DR: The effect of the cdc1-100 mutation on recombinational double-strand break repair indicates that a recombinationally silent mechanism other than sister chromatid exchange was responsible for the efficient repair of DNA double-Strand breaks.
Abstract: To isolate Saccharomyces cerevisiae mutants defective in recombinational DNA repair, we constructed a strain that contains duplicated ura3 alleles that flank LEU2 and ADE5 genes at the ura3 locus on chromosome V. When a HO endonuclease cleavage site is located within one of the ura3 alleles, Ura+ recombination is increased over 100-fold in wild-type strains following HO induction from the GAL1, 10 promoter. This strain was used to screen for mutants that exhibited reduced levels of HO-induced intrachromosomal recombination without significantly affecting the spontaneous frequency of Ura+ recombination. One of the mutations isolated through this screen was found to affect the essential gene CDC1. This mutation, cdc1-100, completely eliminated HO-induced Ura+ recombination yet maintained both spontaneous preinduced recombination levels and cell viability, cdc1-100 mutants were moderately sensitive to killing by methyl methanesulfonate and gamma irradiation. The effect of the cdc1-100 mutation on recombinational double-strand break repair indicates that a recombinationally silent mechanism other than sister chromatid exchange was responsible for the efficient repair of DNA double-strand breaks.
TL;DR: Purnark, a mixture of extracts of turmeric, betel leaf and catechu, was tested for its chemoprotective activity against BP induced DNA damage and gave 50‐60 % protection againstBP induced SCEs and micronuclei.
TL;DR: The comparative induction of chromatid aberrations by 238Pu alpha-particles, or by 250 kVp X-rays was investigated in V79 Chinese hamster cells, suggesting increased multiple lesion interaction.
Abstract: The comparative induction of chromatid aberrations by 238Pu alpha-particles, or by 250 kVp X-rays was investigated in V79 Chinese hamster cells. Metaphases were sampled at hourly intervals postirradiation up to 8 h and BrdU/FPG staining methods were used to distinguish G2, S and G1 phase cells. Two experiments were performed. In the first, an alpha-particle dose of 0.41 Gy was compared with an X-ray dose of 1.5 Gy used in a previously published study. In the second, an X-ray dose of 1.2 Gy was used in parallel with 0.41 Gy of alpha-particles to produce a similar overall frequency of interchanges, and allow comparative ratios to be derived for other aberration types. At these isoexchange doses, alpha-particles produce relatively less gaps and breaks, particularly in late G2, and significantly more isochromatid deletions. A very high proportion of the isochromatid deletions were incomplete after alpha-particles compared with X-rays, but no difference in incompleteness was found for interchanges. With X-rays, about 6% of interchanges are complex intra-interchange forms. At similar exchange frequencies this increases to 26.7% for alpha-irradiation, suggesting increased multiple lesion interaction. Differences in dose distribution between alpha-particles and X-rays are discussed and mitotic delay is examined after separation of the analysed cells into damaged and undamaged classes.
TL;DR: The results suggest that the HLA region is hyperrecombinogenic in somatic cells and that the elevated recombination rate in BS cells results from the general increase at ordinary sites and not from random creation of unusual sites for recombination.
Abstract: Bloom's syndrome (BS) is an autosomal recessive disorder conferring high propensity for cancer and displaying a high degree of genetic instability; the frequency of sister chromatid exchange is characteristically 10 times above background. The symmetrical four-armed chromatid interchanges are much more readily detected in peripheral blood lymphocytes of BS patients, suggesting that the frequency of somatic recombination is also increased. In the present study, the rate of spontaneous loss of HLA-A allele expression was estimated following fluctuation analysis in cultured T lymphocytes using a flow-cytometric assay. It was found to be 10 times or more higher than normal in lymphocytes from a BS patient. Molecular and chromosome analyses showed that all 13 independent variants from the patient were most likely derived from somatic recombinations. Further tests for loss of heterozygosity at a closely linked proximal locus, HLA-DQA1, showed that as many as half of the recombinants retained heterozygosity irrespective of the donor. The results suggest that the HLA region is hyperrecombinogenic in somatic cells and that the elevated recombination rate in BS cells results from the general increase at ordinary sites and not from random creation of unusual sites for recombination.
TL;DR: Among both the exposed workers and the controls, smokers had a higher SCE frequency than non-smokers, and smoking habit was the other factor most influencing SCE levels.
Abstract: Car painting workers are exposed to a number of potentially genotoxic agents. The frequencies of sister chromatid exchanges (SCEs) were determined in a group of 22 workers involved in painting repaired cars in small workshops. An occupationally non-exposed age-matched group served as controls. There was a significant difference (P < 0.001) in the mean SCE levels in exposed (7.81 +/- 1.50) and non-exposed (4.92 +/- 0.10) groups. Smoking habit was the other factor most influencing SCE levels. Among both the exposed workers and the controls, smokers had a higher SCE frequency than non-smokers.
TL;DR: It should be investigated whether UV-disinfection of natural and contaminated organic substances in surface and drinking water may generate a positive mutagenic effect.
TL;DR: Very low quantities of substances corresponding to airborne particulates from less than 1 m3 air were highly effective in both cell systems, and tracheal epithelial cells of the Syrian golden hamster revealed a higher sensitivity showing a steeper increase of 'sister chromatid exchanges' than human lymphocytes.
TL;DR: The results confirm in vivo cell cycle phase specificity of the drug and designate etoposide as a potent clastogen and a genotoxic agent in mice.
Abstract: Etoposide (VP 16-213), the epipodophyllotoxin derivative that is widely used in the treatment of cancer, forms complexes with DNA-topoisomerase type II alpha to exert its cytotoxicity. The drug was evaluated in vivo in Swiss albino mouse bone marrow cells for its ability to induce clastogenicity and sister chromatid exchanges (SCEs). Doses of 5, 10, 15, and 20 mg/kg body weight etoposide given intraperitoneally induced a dose-dependent significant increase of clastogenicity (Trend test, alpha < or = 0.05). The aberrations induced were predominantly chromatid types. The drug shows specificity for S-phase cells: cells harvested 6 and 12 hr posttreatment showed a significantly increased number of damaged cells and aberrations per cell. Doses of 0.5, 1.0, 2.5, 5.0, and 10.0 mg etoposide/kg body weight induced a dose-dependent significant induction of SCEs (Trend test, alpha < or = 0.05). The minimal effective concentration was 0.5 mg/kg body weight. Etoposide significantly prolonged the cell cycle time at all concentrations tested: 12-13 hr in treated animals vs. 11 hr in control. The results confirm in vivo cell cycle phase specificity of the drug and further designate etoposide as a potent clastogen and a genotoxic agent in mice.