Showing papers on "Sister chromatid exchange published in 1981"
TL;DR: The data support the concept that SCEs provide a useful indication of exposure, although the mechanism and biological significance of SCE formation still remain to be elucidated.
Abstract: This paper reviews the ability of a number of chemicals to induce sister-chromatid exchanges (SCEs). The SCE data for animal cells in vivo and in vitro, and human cells in vitro are presented in 6 tables according to their relative effectiveness. A seventh table summarizes what is known about the effects of specific chemicals on SCEs for humans exposed in vivo. The data support the concept that SCEs provide a useful indication of exposure, although the mechanism and biological significance of SCE formation still remain to be elucidated.
576 citations
TL;DR: It is reported here that PMA, but not its weakly or non-promoting derivatives, induced chromosomal aberrations with high efficiency in phytohaemagglutinin (PHA)-stimulated human lymphocytes, but was only a weak producer of SCE.
Abstract: The mouse skin tumour promoter phorbol-12-myristate-13-acetate (PMA) does not form covalent adducts with cellular DNA and its mutagenic potency in several systems is low or absent1–6. There have been conflicting reports of the capacity of PMA to produce sister chromatid exchanges (SCEs)3,6–8. As PMA induces the formation of superoxide radicals in polymorphonuclear leukocytes and mitogen-stimulated lymphocytes9–11, we suggested that it might produce DNA damage via indirect action by the formation of intermediate active oxygen species12,13. As is typical for other DNA-damaging agents which mainly act indirectly, for example, ionizing radiation, PMA would be expected to have low mutagenicity but high clastogenic (chromosome-breaking) activity14. In agreement with this, we report here that PMA, but not its weakly or non-promoting derivatives, induced chromosomal aberrations with high efficiency in phytohaemagglutinin (PHA)-stimulated human lymphocytes, but was only a weak producer of SCE. This activity was suppressed by superoxide dismutase, which catalyses the breakdown of superoxide radicals.
197 citations
TL;DR: It has been suggested that the SCE-technique should be considered as a valuable additional method for cytogenetic mutagenicity testing, which is not adequate to replace the classical methods of analysis of structural chromosome damage.
Abstract: Data from previous studies published on the induction by mutagens of sister chromatid exchanges (SCEs) and structural chromosome damage were compared qualitatively and quantitatively. Although a good correlation between the incidence of both cytogenetic phenomena has been pointed out in many previous publications, about 30% of the agents for which comparable data were available yielded non-corresponding qualitative results concerning both indicator effects. However, even in the group with good qualitative agreement distinct quantitative differences indicated different molecular mechanisms of the formation of SCEs and breaks. Additional information supporting the importance of these differences for the validity of both indicator systems has been derived from the results obtained using strong clastogens exhibiting a low or no SCE-inducing activity and vice versa, from special observations on chromosomal breakage syndromes, and from studies on the action of known co- and anti-clastogens on SCE-induction by chemical mutagens. As a result, it has been suggested that the SCE-technique should be considered as a valuable additional method for cytogenetic mutagenicity testing, which, however, is not adequate to replace the classical methods of analysis of structural chromosome damage.
171 citations
TL;DR: The search for evidence of SCEs at a MOLECULAR level and the enzymology of seE Formation and the relationships to DNA Replication Fork are described.
Abstract: INTRODUCTION 11 INFORMATION ABOUT CHROMOSOME ORGANIZATION PROVIDED BY SCE ANALYSIS 12 SCE INDUCTION 15 SeE Induction by Diff erent Types of DNA Damage 16 Duration of the SCE Response 22 Modulation of the seE Response 23 CORRELATES OF SCEs ........ 32 Chromosome Breaks 32 Somatic Recombination 33 Meiotic Recombination 33 Somatic Mutation 33 Effects on Integrated DNA Sequences 34 THE SEARCH FOR EVIDENCE OF SCEs AT A MOLECULAR LEVEL ........ 35 FUTURE PROSPECTS 36 Sequences that Might Mediate DNA Interchange 36 The Relationship of SCE Formation to the DNA Replication Fork 37 The Enzymology of seE Formation 38 Comporison Between Gene Copy Number Change and SCE Formation 38 BIOLOGICAL IMPORTANCE OF SeEs 40 SUMMARY 42
169 citations
TL;DR: The induction of SCE and chromosomal aberrations by metals reemphasizes the sensitivity of cytological assays and their importance for detecting genetic damage caused by carcinogens.
Abstract: Sister chromatid exchange (SCE) and chromosome aberration induction were determined for several inorganic metal salts. Arsenic, nickel, and beryllium salts at concentrations effective in causing transformation of Syrian hamster cells (HEC) induced SCE and chromosome aberrations of HEC and human lymphocytes, whereas sodium tungstate, a non-transforming chemical, neither induced SCE nor chromosome aberrations. Normal human and hamster cells exhibited equal sensitivity to SCE induction; nontoxic concentrations of sodium arsenite, beryllium sulfate, and nickel sulfate caused an increase of 8-10 SCE/cell over control values. Sodium arsenite, a trivalent arsenic, and sodium arsenate, a pentavalent arsenic, produced increases in SCE but the former was effective at lower concentrations. Both arsenic salts were less efficient in inducing SCE in human whole blood than in purified lymphocyte cultures. Sodium arsenite, sodium arsenate, nickel sulfate, and beryllium sulfate also caused damage consisting primarily of chromatid type of aberrations. In HEC, with doses most effective in SCE induction , all four metals produced aberrations in 16-21% of cells. In human lymphocytes, 34 and 30% of the cells had chromosome damage after sodium arsenite and sodium arsenate, respectively, whereas beryllium sulfate or nickel sulfate caused damage in about 10% of the cells. The induction of SCE andmore » chromosomal aberrations by metals reemphasizes the sensitivity of cytological assays and their importance for detecting genetic damage caused by carcinogens.« less
127 citations
TL;DR: It was found that the presence of inhibitor even in the first cell cycle increased the frequencies of SCEs, and it was concluded that the incorporated BrdUrd plays an important role in the origin of spontaneous and induced S CEs.
Abstract: 3-Aminobenzamide and benzamide, two potent inhibitors of poly-(ADP-ribose)-polymerase increase the frequencies of SCEs in Chinese hamster ovary cells in a dose-dependent manner. SCEs were studied in cells in which the inhibitors were present either during the first cell cycle or the second cell cycle or both. Most of the induced SCEs were found to be formed during the second cell cycle in which BU-containing DNA was used as template for DNA synthesis. In cells which were pregrown for 4 cell cycles in the presence of BrdUrd, in order to obtain both sister chromatids bifiliarly substituted with BU in their DNA, it was found that the presence of inhibitor even in the first cell cycle increased the frequencies of SCEs. It is concluded that the incorporated BrdUrd plays an important role in the origin of spontaneous and induced SCEs. 3-Aminobenzamide alone or benzamide in the presence of BrdUrd during culture, did not increase the frequencies of mutations to HGPRT- in these cells.
119 citations
TL;DR: It is speculated that BS cells are deficient in the detoxification of active oxygen species, similar to certain collagen diseases such as systemic lupus erythematosus.
Abstract: Media from cultures of fibroblasts of six patients with the autosomal recessive disease Bloom syndrome (BS) and from four normal fibroblast strains were analyzed for clastogenic activity towards phytohemagglutinin-stimulated human blood lymphocytes from healthy donors. Clastogenic activity was detected in concentrated ultrafiltrates of media from all six BS strains but none of the normal fibroblast strains. The frequencies of chromosomal aberrations that were induced depended on the concentration of the ultrafiltrates. Addition of bovine superoxide dismutase to the blood lymphocyte cultures strongly suppressed the clastogenic potency of the ultrafiltrates. Unconcentrated conditioned BS media were inactive. From the pore size of the ultrafilters and Sephadex G-10 chromatography it is concluded that the clastogenic material is in the molecular weight range of 1000 to 10,000. The concentrated ultrafiltrates of BS culture media also possessed the capacity to induce sister chromatid exchanges in normal human blood lymphocytes, but with relatively low efficiency. On the basis of these results and by analogy to certain collagen diseases such as systemic lupus erythematosus, we speculate that BS cells are deficient in the detoxification of active oxygen species.
109 citations
TL;DR: Findings suggest that the aging environment may not play a major role in the diminished SCE induction observed in old cell populations, and that normal bone marrow cell populations between young and old animals are not significantly different.
88 citations
TL;DR: The eastern mudminnow, U. pygmaea, appeared to be a useful test animal for the detection of the cytogenetic effects of chemical pollution in the aquatic environment and an effect was found on the frequency of both sister chromatid exchange and chromosome aberrations.
76 citations
TL;DR: Baseline sister chromatid exchanges increase as a function of average replicon size in a variety of human and Chinese hamster cell lines, and this observation is the basis for a model in which SCEs are generated by errors in the unravelling of daughter double helices by topo isomerases.
72 citations
TL;DR: The rate of cell proliferation appears to be an important determinant of the SCE-frequency in conventional lymphocyte cultures, and it appears less likely that B and T cells constitute these tentative subpopulations.
Abstract: Human B and T lymphocytes differ in the rate of cell proliferation and frequency of sister chromatid exchange (SCE) when cultured separately in short-term cultures. This difference could theoretically be responsible for part of the variation in the SCE-frequency previously observed among healthy subjects since there is individual variation in the proportion of B and T cells in the peripheral blood. We have therefore studied cell proliferation and SCE-frequency in conventional short-term cultures of lymphocytes from 28 healthy subjects with different proportions of B and T cells. The percentage, of B or T lymphocytes did not correlate with the SCE-frequency, nor with the rate of cell proliferation in culture. However, a significantly higher SCE-frequency was found in slowly proliferating cultures than in cultures with a high rate of turn over. Thus, the rate of cell proliferation appears to be an important determinant of the SCE-frequency in conventional lymphocyte cultures. Although the data do not exclude attribution of the difference in SCE-frequency between rapidly and slowly growing cultures to differences in subpopulations of lymphocytes, it appears less likely that B and T cells constitute these tentative subpopulations.
Journal Article•
TL;DR: The bromodeoxyuridine differential chromatid labeling techniques were applied and permits in vivo assessment of induction of DNA damage by SCE analysis as well as inhibition of cellular replication by specific cancer chemotherapeutic agents in tumor and normal cell populations.
Abstract: The bromodeoxyuridine differential chromatid labeling techniques were applied to the simultaneous in vivo examination of cell cycle kinetics and sister chromatid exchange (SCE) induction by various cancer chemotherapeutic agents in normal and Ehrlich ascites tumor cell populations. Compounds which yielded high ratios of SCE (in tumor cells):SCE (in normal cells) also produced greater inhibition of cellular replication in tumor cells when compared to normal cells. Thus, this approach permits in vivo assessment of induction of DNA damage by SCE analysis as well as inhibition of cellular replication by specific cancer chemotherapeutic agents in tumor and normal cell populations.
TL;DR: Indirect evidence implies that 8-azaguanine-resistant (AGr) lymphocytes in human peripheral blood are mutants associated with the loss of the hypoxanthine–guanine phosphoribosyltransferase (HPRT) locus on the active X chromosome, the mutation frequency increasing linearly with age.
Abstract: Indirect evidence implies that 8-azaguanine-resistant (AGr) lymphocytes in human peripheral blood are mutants associated with the loss of the hypoxanthine–guanine phosphoribosyltransferase (HPRT) locus on the active X chromosome, the mutation frequency increasing linearly with age. AGr variants are readily induced in lymphocytes exposed to mitomycin C in vitro, their incidence correlating with induced sister chromatid exchanges (SCEs). Although SCE events and the development of an AGr phenotype may reflect a common type of DNA damage, mitomycin C-induced AGr variants are not mutants but are suggested to be cells having a transcriptional block at the HPRT locus. AGr variants are also readily induced by X rays in vitro, their incidence correlates closely with the incidence of aberrations induced in the X chromosome and they are considered to have a mutational origin.
TL;DR: Results suggest that trivalent arsenic is more genotoxic than pentavalent arsenic and that arsenic exerts its effect mainly during cell division.
Abstract: Cultured human lymphocytes were exposed to trivalent (NaASO2) and pentavalent (Na2HAsO4) arsenic in concentrations comparable to the arsenic levels found in the urine of copper smelter workers. Significantly increased frequencies of chromosome aberrations (gaps, chromatid breaks, chromatid exchanges and chromosome breaks) were found after exposure to trivalent but not pentavalent arsenic. This effect was not found when nonstimulated (GO) lymphocytes were exposed to trivalent arsenic and then cultured. The rate of sister chromatid exchanges was also found to be increased after exposure to trivalent arsenic. Thus results suggest that trivalent arsenic is more genotoxic than pentavalent arsenic and that arsenic exerts its effect mainly during cell division.
TL;DR: Spontaneous and UV induced unequal mitotic sister chromatid recombination was examined in RAD+ and rad52-1 strains carrying the LEU2 gene inserted in the rDNA locus and the rad 52-1 mutation greatly reduces the frequency of UV induced sister chromate recombination.
Abstract: Spontaneous and UV induced unequal mitotic sister chromatid recombination was examined in RAD+ and rad52-1 strains carrying the LEU2 gene inserted in the rDNA locus. The rad52-1 mutation does not affect spontaneous sister chromatid recombination but greatly reduces the frequency of UV induced sister chromatid recombination.
TL;DR: This rat lymphocyte culture system provides a reliable means of investigating chemically induced SCE in the rat and is recommended to maintain low baseline SCE levels and to avoid cytotoxicity.
Abstract: Lymphocyte culture systems have the major advantage of permitting the analysis of in vivo cytogenetic damage with minimal injury to the animal under study. This paper describes a rat lymphocyte culture system designed for the study of sister chromatid exchange (SCE) induced by in vivo exposure to genotoxic agents. A standard protocol was established in which 1 to 2 ml of blood are removed from rats by cardiac puncture, washed three times with phosphate-buffered saline (pH 7.4), and grown in RPMI 1640. 5-Bromodeoxyuridine (BrdU) (1.0 microM) is added after 24 hr, and cells are harvested after 56 hr of culture. Critical steps for successful blast transformation include washing the blood in buffered saline and the adding of 2.0 to 4.0 microgram phytohemagglutinin/ml to the culture medium. The use of low concentrations of BrdU (less than or equal to 5.0 microM) is recommended to maintain low baseline SCE levels and to avoid cytotoxicity. The mutagenic carcinogen, ethyl methanesulfonate (EMS), was used as a positive control agent and at a dose of 300 mg/kg caused a fourfold increase in SCE frequency. Twenty-eight days after EMS administration (30, 100, 300 mg/kg), lymphocytes from treated animals still displayed SCE levels at least 50% above baseline. This system provides a reliable means of investigating chemically induced SCE in the rat.
TL;DR: The positive linear correlation between chemical carcinogen‐induced SCE and transformation suggests a relationship between the two cellular responses, and BP was the least effective carcinogen.
Abstract: Sister chromatid exchange (SCE) and morphological transformation induced by five chemical carcinogens, N-acetoxy-2-fluorenyl-acetamide (AcAAF), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), benzo[a]-pyrene (BP), and cisplatinum(II) diamine dichloride (PT) as well as by X-irradiation were quantified in parallel experiments with cultures of Syrian hamster embryo cells (HEC). Incubation of HEC with 5-bromodeoxyuridine (10(-5)M) for two rounds of replication (24 h) required for SCE visualization neither caused morphological transformation nor altered the transformation frequency induced by carcinogen alone. All chemical carcinogens, but not X-irradiation, produced a dose-dependent increase in SCE and transformation frequency, demonstrating the sensitivity of both assays to carcinogens. The ratios of induced SCE relative to transformation frequency, however, varied with the carcinogen. BP, MMNG, and AcAAF were similarly efficient in inducing SCE compared to transformation but were considerably less effective than MMS and PT. X-irradiation at doses of 200, 300, and 500 R did not cause transformation and induced a low frequency of SCE. On a molar basis, MMS and PT were the most effective in SCE induction relative to transformation, MNNG and AcAAF were less effective, and BP was the least effective carcinogen. The positive linear correlation between chemical carcinogen-induced SCE and transformation suggests a relationship between the two cellular responses.
TL;DR: The results suggest that free radicals, particularly the superoxide anion, may be important intermediates in some of the biologic effects of TPA.
Abstract: The induction of sister chromatid exchanges (SCE) by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was measured in mouse 10T1/2 and 3T3 cells released from density; inhibition, and Chinese hamster CHO cells synchronized by mitotic selection. The induced frequency of SCE was similar in each cell type, but depended upon the concentration of TPA employed, its source, and the particular lot from the same source. Most SCE occurred in the first two rounds of cell replication after addition of TPA. The induction of SCE by TPA was markedly suppressed if the fetal calf serum in the incubation medium was not heat-inactivated. The addition of superoxide dismutase to medium with heat-inactivated serum also suppressed the induction of SCE. These results suggest that free radicals, particularly the superoxide anion, may be important intermediates in some of the biologic effects of TPA.
TL;DR: It is concluded that the well-established value of clinical ultrasonography warrants its continued use; however, minimizing the numbers and lengths of exposure per patient would seem prudent, pending further information on clinical implications of the authors' results.
Abstract: We analyzed sister chromatid exchange (SCE) frequencies as an indicator of DNA damage induced in human lymphocytes by ‘real-time’ ultrasound. A range of exposure times and intensities was tested in a series of blind, randomized, in vitro experiments under spatial and sonographic conditions simulating exposure of a gravid abdomen and uterus. Our studies showed small but consistent effects of ultrasound on SCE frequencies, for each experiment. Differences between matched control and exposed means were significantly different from zero. X2 tests for homogeneity indicated no significant differences among either the means or the total distributions of the controls, nor among each of the separate dose levels. Consequently, experiments were pooled, and X2 analysis indicated significant differences both among distributions and among means of SCE frequencies for controls versus exposed cells (P(0.001). The pooled control mean was also significantly different from each of the pooled dose means. Correcting for multiple comparisons gave identical results for the paired comparisons of means except for the 20-min level which was borderline (0.025P(0.01). We conclude that the well-established value of clinical ultrasonography warrants its continued use; however, minimizing the numbers and lengths of exposure per patient would seem prudent, pending further information on clinical implications of our results.
TL;DR: The gas-exposure apparatus used in this experiments seems to be useful for quantitative investigation of the effects of various gaseous materials on cultured mammalian cells or bacterial cells.
Abstract: Effects of gaseous nitrogen dioxide (NO2) on chromosomal morphology of cultured Chinese hamster V79-H3 cells were investigated. Chinese hamster cells were exposed to NO2 gas in N2 gas at NO2 concentrations of 0, 5, 10, 20, 50 and 100 ppm (v/v) for 10 min at a gas flow rate of 1000 ml/min. Both chromosomal aberrations and sister-chromatid exchanges were increased depending on the NO2 concentration. The effects of sodium nitrite (NaNO2) were also examined in comparison with those of gaseous NO2, and it was found that the effects of gaseous NO2 could not be ascribed to those of nitrous acid. The gas-exposure apparatus used in this experiments seems to be useful for quantitative investigation of the effects of various gaseous materials on cultured mammalian cells or bacterial cells.
01 Jan 1981
TL;DR: Higher plants provide valuable systems for screening and monitoring environmental chemicals, but a general lack of familiarity with plant mutagenesis research, and the belief that plant and animal cells diverge so greatly in their physiology and phylogeny as to make comparisons meaningless, has led to a dearth of interest in, and funding for, plant Mutagenesis.
Abstract: Higher plants provide valuable systems for screening and monitoring environmental chemicals. Although plant screening and monitoring assay systems have been in existence for many years, they are only beginning to receive the recognition which these sensitive and reliable systems warrant (de Serres, 1978). A general lack of familiarity with plant mutagenesis research, and the belief that plant and animal cells diverge so greatly in their physiology and phylogeny as to make comparisons meaningless, has led to a dearth of interest in, and funding for, plant mutagenesis. Recent symposia on the subject (Hart et al., 1978; de Serres, 1978) may help improve the situation.
TL;DR: The results of these studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.
Abstract: Diethylstilbestrol diphosphate (DES-dp) clastogenesis was examined in the bone marrow of C57B1/6 male and female mice. Significant and sex-related dose effects were observed for the induction of chromatid-type chromosomal aberrations and for the inhibition of cellular proliferation. Females were more sensitive to the effects of DES-dp than males when assessed for either induced chromosomal aberrations or proliferative inhibition. Contrary to other published results, we did not observe either an increase in sister chromatid exchanges or an increased incidence of aneuploidy. Ovariectomy reduced the ability of DES-dp to inhibit cellular proliferation and decreased the high degree of variability between animals at high doses of DES-dp. The results of our studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.
TL;DR: A significantly higher frequency of baseline sister chromatid exchange was found in the cultured lymphocytes of 13 Blackfoot disease patients in comparison with that of healthy persons (HP), and sodium arsenite was found to be effective in increasing the SCE frequency and delaying the cell growth of the lymphocytes from both BFP and HP.
Abstract: A significantly higher frequency of baseline sister chromatid exchange (SCE) was found in the cultured lymphocytes of 13 Blackfoot disease patients (BFP) in comparison with that of healthy persons (HP). Twelve of these BFP consumed well water containing a high concentration of arsenic for 15 years or longer and had switched to drinking tap water 12 years before the time of this study. Sodium arsenite was found to be effective in increasing the SCE frequency and delaying the cell growth of the lymphocytes from both BFP and HP. However, the SCE increment induced by sodium arsenite as well as the progression of the cell divisions in the cultured lymphocytes showed no significant difference between BFP and HP.
TL;DR: Fertility and sperm number, motility, and morphology were analyzed in male C57BL/6 mice exposed to various mixtures of 2,4-dichlorophenoxyacetic acid, and Somatic cell (bone marrow) sister chromatid exchange frequencies were also evaluated in mice injected with similar chemical mixtures.
Abstract: Fertility and sperm number, motility, and morphology were analyzed in male C5 7BLJ6 mice exposed to various mixtures of 2,4‐dichlorophenoxyacetic acid (2,4‐D), 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T), and 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in the diet for 8 wk. Somatic cell (bone marrow) sister chromatid exchange frequencies were also evaluated in mice injected with similar chemical mixtures. The concentration of the test chemicals was such that the average daily feeding dose in the three mixtures or control was 40 mg/kg 2,4‐D, 40 mg/kg 2,4,5‐T, and 2.4 μg/kg TCDD; 40 mg/kg 2,4‐D, 40 mg/kg 2,4,5‐T, and 0.16 μg/kg TCDD; 20 mg/kg 2,4‐D, 20 mg/kg 2,4,5‐T, and 1.2 μg/kg TCDD; or no chemical added (control). No significant dose‐related effects were observed in the treated mice compared to the control group.
TL;DR: Cyclophosphamide appears to require maternal metabolic activation in order to cause an increased SCE frequency in yolk sac cells, and the system described permits versatile SCE analyses which can help to define relative maternal and embryo tissue-specific sensitivities to chemical-induced genetic damage.
Abstract: Sister-chromatid exchange (SCE) analyses were conducted in maternal, embryonic and extraembryonic tissues of pregnant rats and mice. The various tissues were substituted in vivo with 5-bromodeoxyuridine (BrdU) by implantation of a BrdU tablet in pregnant animals at mid-gestation. Following maternal exposure to 5–20 mg/kg cyclophosphamide, embryonic liver cells demonstrated dose-dependent SCE increases up to 10-fold that of control. Rat embryos revealed little intralitter variability for this transplacental effect. Maternal marrow and yolk sac cells examined in the rat also underwent significant increases in SCE, although to different extents. While marrow SCE frequencies were similar to those of embryo liver, yolk sac SCE frequencies were generally much lower. SCE analyses were also conducted in rat yold sac cells substituted in vivo with BrdU and subsequently explanted to whole-embryo culture. In vitro exposure to cyclophosphamide at concentrations up to 100 μg/ml had no SCE-inducing effect. However, similar exposures to phosphoramide mustard, a presumed metabolite of cyclophosphamide, caused dose-dependent increases in SCE up to 8-fold higher than control at 2 μg/ml. Thus, cyclophosphamide appears to require maternal metabolic activation in order to cause an increased SCE frequency in yolk sac cells. The system described permits versatile SCE analyses which can help to define relative maternal and embryo tissue-specific sensitivities to chemical-induced genetic damage.
TL;DR: It is proposed that aniline may exert its tumorigenic potential in rats through the production of both genotoxic and cytotoxic metabolites as well as a less clear-cut, dose-related increase in SCE frequency with a 1.4-fold elevation.
Abstract: Sister chromatid exchange (SCE) and cell cycle analyses in human fibroblasts were used to ascertain the relative genotoxicity and cytotoxicity of aniline and its metabolites. Fibroblasts were allowed to attach to plastic petri dishes for 4 hr and exposed in serum-free medium for 2 hr to the following: aniline HCl (0.05–10.0 mM), acetanilide (0.1–10.0 mM), o-hydroxyacetanilide (0.01–2.0 mM), p-hydroxyacetanilide (0.1–10.0 mM), o-aminophenol (0.01–0.3 mM), p-aminophenol (0.005–0.2 mM), N-phenylhydroxylamine (0.001–0.5 mM). Triethylenemelamine (TEM; 0.25 and 0.49 μM) was used as a positive control. The treatment medium was replaced with complete medium containing 5-bromo-deoxyuridine (10 μM), and cells were allowed to grow for 48 hr with Colcemid present for the final 4.5 hr. Cell cycle analyses (percentage of cells in first, second, or third division) revealed that p-hydroxyacetanilide (10mM), p-aminophenol (≥0.1 mM), o-aminophenol (≥0.1 mM), N-phenylhydroxylamine (≥ mM), and TEM (0.49 μM) inhibited cell proliferation. Cell death was seen at doses of 0.5 mM N-phenylhydroxylamine, 0.2 mM p-aminophenol, and 0.3 mM o-aminophenol. Significant increases (P0.05) in SCE frequencies were found with aniline HCl, o-aminophenol, N-phenylhydroxylamine, and TEM. On an SCE/mmole basis at the highest concentrations examined, o-aminophenol was 270 times more potent than aniline in inducing SCE, whereas TEM was about 390 times more potent than o-aminophenol. Furthermore, fibroblasts treated with o-aminophenol responded in a dose-dependent fashion and exhibited a 2-fold increase in SCE frequency. N-phenylhydroxylamine induced a less clear-cut, dose-related increase in SCE frequency with a 1.4-fold elevation. Only marginal increases in SCE were observed with aniline at the highest doses. Using these data, we propose that aniline may exert its tumorigenic potential in rats through the production of both genotoxic and cytotoxic metabolites.
Journal Article•
TL;DR: Results indicate that, while sister chromatid exchanges may be useful as indicators of primary carcinogen mutagens, they may have little utility when secondary agents after the response of cells to a primary initiator.
Abstract: Modification of sister chromatid exchanges and radiation-induced transformation in mouse C3H/10T1/2 and Syrian hamster embryo cells by the tumor promoter 12- O -tetradecanoylphorbol-13-acetate and two retinoids, the trimethylmethoxy-phenyl analog of N -ethyl retinamide and β-all- trans -retinoic acid, has been studied. 12- O -tetradecanoylphorbol-13-acetate alone enhances, and retinoids alone reduce radiation-induced transformation. When both compounds were present, the retinoids not only reduced the oncogenic effects of radiation but completely eliminated the promoting effects of 12- O -tetrade-canoylphorbol-13-acetate. These results were not paralleled by changes in sister chromatid exchange frequencies, indicating that, while sister chromatid exchanges may be useful as indicators of primary carcinogen mutagens, they may have little utility when secondary agents alter the response of cells to a primary initiator.
TL;DR: The Saccharomyces cerevisiae D3 recombinogenic assay, the assay for forward mutagenesis in L5178Y mouse lymphoma cells, and the sister chromatid exchange assay using Chinese hamster ovary cells were used to evaluate the in vitro mutagenic and DNA-damaging effects of eight samples of diesel engine emissions and related environmental emissions.
TL;DR: Fusion of fresh lymphocytes from a Bloom syndrome patient with those of normal subjects or a BS heterozygote resulted in complete normalization of the frequency of sister chromatid exchanges in the chromosomes of BS cells, compatible with the concept that BS is a recessive genetic mutation at regulatory levels of the DNA repair function.
Abstract: Fusion of fresh lymphocytes from a Bloom syndrome (BS) patient with those of normal subjects or a BS heterozygote resulted in complete normalization of the frequency of sister chromatid exchanges in the chromosomes of BS cells. This normalization took place by the first mitosis in hybrid cells. In contrast, cultivation of BS lymphocytes with those of normal subjects or the BS heterozygote had no effect on sister chromatid exchanges. The cell fusion experiments suggest that the normalization on the sister chromatid exchanges. The cell fusion experiments suggest that the normalization of the sister chromatid exchange frequencies in BS cells can be achieved by factors conserved in the cells of various mammalian species. These findings are compatible with the concept that BS is a recessive genetic mutation at regulatory levels of the DNA repair function.
Journal Article•
TL;DR: The scored frequency of transformation and appearance of the oncogenic marker "long microvilli" in mouse embryo fibroblast C3H/10T 1/2 cells in culture for the compound Ni3S2 and the increased sister chromatid exchange in cultured human lymphocytes may indicate that the carcinogenic effect of Ni2S2 is genetic rather than epigenetic.
Abstract: We have scored frequency of transformation and appearance of the oncogenic marker “long microvilli” in mouse embryo fibroblast C3H/10T½ cells in culture for the compound Ni 3 S 2 . Furthermore, we have scored for Ni 3 S 2 -induced sister chromatid exchange in cultured human lymphocytes. Nickel subsulfide in moderate doses caused morphological transformation to type I, II, and III foci and induced long microvilli on the cells in the transformed cultures, demonstrating oncogenic transforming ability. Higher doses led to cell lysis after a lag period. The carcinogenic potency of Ni 3 S 2 in this system was not as strong as that of methylcholanthrene. Ni 3 S 2 increased the sister chromatid exchange frequency in human lymphocytes in a marginal, not dose-dependent way. The increased sister chromatid exchange may indicate that the carcinogenic effect of Ni 3 S 2 is genetic rather than epigenetic.