Showing papers on "Sister chromatid exchange published in 1988"
TL;DR: No statistically significant influence was found of age or sex, nor of any other parameter tested, on the frequency of any chromosomal aberration type, with the single exception of long acentric fragments, often "supernumerary" believed to represent X chromosomes precociously separated at the centromere.
Abstract: In order to assess the potential of cytogenetic determinations on peripheral blood lymphocytes as a means of monitoring human populations subject to low level occupational and environmental exposures to chemical mutagens and carcinogens, accurate baseline data are required. Accordingly, we have determined mean frequencies of chromosomal aberrations and of sister-chromatid exchanges, their variances, and the sources of this variance in a cohort of 353 healthy employees of the Brookhaven National Laboratory. A detailed protocol was adopted for blood sampling, lymphocyte culture, cytogenetic preparation and scoring in order to minimize variation from these potential sources. Scoring was divided between the Oak Ridge and the Brookhaven groups with duplicate scoring sufficient to evaluate and minimize the effect of any differences between laboratories or between individual scorers. In all, the data include 71,950 cells scored for chromosomal aberrations and 16,898 cells scored for sister-chromatid exchanges. The mean unadjusted frequency of sister-chromatid exchanges was 8.29 +/- 0.08/cell. As reported in other studies, cigarette smoking very significantly influenced sister-chromatid exchange frequencies; in our study the mean for smokers was 9.0 +/- 0.2, while that for non-smokers was 8.1 +/- 0.1/cell. The mean frequency was statistically higher in females than in males, regardless of smoking status. On the other hand, age of the subject did not significantly influence sister-chromatid exchange frequencies. Curiously, the subject's total white cell count did influence sister-chromatid exchange frequency. No other source of variation was found. The frequencies of chromosomal aberrations of all types were determined. The frequency of the most common unequivocal chromatid type, the chromatid deletion, was 0.81 +/- 0.05%, that of the most common unequivocal chromosome type, the dicentric, was 0.16 +/- 0.02%. No statistically significant influence was found of age or sex, nor of any other parameter tested, on the frequency of any chromosomal aberration type, with the single exception of long acentric fragments, often "supernumerary", believed to represent X chromosomes precociously separated at the centromere. Such fragments were significantly more frequent in samples from females than those from males, and showed a significant positive regression on age.
233 citations
TL;DR: It is found that all the dis mutants isolated are supersensitive to caffeine at permissive temperature and suggested that the dis genes are required for the sister chromatid separation at the time of mitosis and that caffeine might affect the dis gene expression.
Abstract: We isolated novel classes of Schizosaccharomyces pombe cold-sensitive dis mutants that block mitotic chromosome separation (nine mapped in the dis1 gene and one each in the dis2 and dis3 genes). Defective phenotype at restrictive temperature is similar among the mutants; the chromosomes condense and anomalously move to the cell ends in the absence of their disjoining so that they are unequally distributed at the two cell ends. Synchronous culture analyses indicate that the cells can enter into mitosis at normal timing but become lethal during mitosis. In comparison with the wild-type mitosis, defects are found in the early spindle structure, the mitotic chromosome structure, the poleward chromosome movement by the spindle elongation and the telophase spindle degradation. The dis mutants lose at permissive temperature an artificial minichromosome at higher rates than occur in the wild type. We found that all the dis mutants isolated are supersensitive to caffeine at permissive temperature. Furthermore, the mutant cells in the presence of caffeine produce a phenotype similar to that obtained at restrictive temperature. We suggest that the dis genes are required for the sister chromatid separation at the time of mitosis and that caffeine might affect the dis gene expression. We cloned, in addition to the dis2+ and dis3+ genes, multicopy extragenic suppressor sequences which complement dis1 and dis2 mutations. A complex regulatory system may exist for the execution of the dis+ gene functions.
210 citations
TL;DR: The data demonstrate the exceptional cytogenetic features of this syndrome: Although the spontaneous and the DEB- and NQO-induced chromosomal breakage rate would suggest that WS is like a classic chromosomal instability syndromes, the lack of sensitivity of WS cells to bleomycin and their stable SCE frequency compared with that of control cells clearly delimitate this syndrome from other entities.
Abstract: In extension of a previous study, spontaneous and clastogen-induced chromosome damage was analyzed in cultures of peripheral blood lymphocytes from six further patients with Werner syndrome (WS) and six healthy controls. In addition, sister chromatid exchange (SCE) was estimated in four of these cases. Lymphocytes of patients with various other diseases were used for another series of control experiments. Diepoxybutane (DEB), 4-nitroquinoline-1-oxide (NQO), and bleomycin (BLM) were the standard clastogens throughout the study. While the spontaneous frequency of chromosomal breakage was significantly higher in lymphocytes from all the patients than in the control cells, the basis SCE rate was un-affected in WS cells. Sensitivity of WS cells to the chromosome-damaging action of BLM did not differ from that of control cells, and their sensitivity to DEB was slightly greater than that of control lymphocytes. However, NQO induced a more distinct increase of both break and interchange aberrations in the WS cells than in control cells or cells from patients with other diseases. This effect was not found for the SCE rate. Our data demonstrate the exceptional cytogenetic features of this syndrome: Although the spontaneous and the DEB- and NQO-induced chromosomal breakage rate would suggest that WS is like a classic chromosomal instability syndromes, the lack of sensitivity of WS cells to bleomycin and their stable SCE frequency compared with that of control cells clearly delimitate this syndrome from other entities.
135 citations
TL;DR: The results indicate that lead compounds may be genotoxic by an indirect mechanism, and lend support to the view that lead is a carcinogen, and demonstrate the importance of different cellular mechanism of metal uptake and bioavailability.
Abstract: We have investigated the activity of insoluble and soluble lead compounds in inducing mutagenesis, cell transformation and sister chromatid exchange in mammalian cells. Insoluble lead sulfide, readily phagocytized, was more than four times as toxic to V79 cells on a microM basis, than two moderately soluble lead compounds although the exposure time for the soluble salts was five times longer. These findings demonstrate the importance of different cellular mechanism(s) of metal uptake and bioavailability. Both insoluble lead sulfide and more soluble lead nitrate were mutagenic at the HPRT locus in V79 cells. Although less mutagenic at the higher concentrations, lead nitrate at a concentration of 500 microM enhanced the mutation frequency greater than 6-fold above background following a 5-day exposure. Although the mechanism(s) by which lead induces mutations is unknown, failure of both compounds to induce SCE and DNA single-strand breaks, detectable by alkaline elution, suggests that lead-induced mutations may not be a result of direct damage to DNA but may occur via indirect mechanisms including disturbances in enzyme functions important in DNA synthesis and/or repair, or in DNA-helical structure. Lead acetate also transformed SHE cells in a dose-response fashion following a 48-h exposure. Our results indicate that lead compounds may be genotoxic by an indirect mechanism, and lend support to the view that lead is a carcinogen.
114 citations
TL;DR: The findings of this presentation suggest that conversion might be an important mechanism for recombination of sister chromatids and possibly for repair of damaged DNA in S or G2.
Abstract: A positive selection system for intrachromosomal recombination in Saccharomyces cerevisiae has been developed. This was achieved by integration of a plasmid containing an internal fragment of the HIS3 gene into its chromosomal location. This resulted in two copies of the HIS3 gene one with a terminal deletion at the 3' end and the other with a terminal deletion at the 5' end. Reversion of the gene disruption could be brought about by plasmid excision, unequal sister chromatid exchange or sister chromatid conversion. The purpose of this study was to define the mechanisms involved in reversion of the gene disruption. The frequency of plasmid excision could be determined by placing a yeast sequence bearing an origin of replication onto the plasmid that was subsequently integrated into the yeast genome. Unequal sister chromatid exchange and conversion could be distinguished by determining the nature of the reciprocal product by Southern blotting. The results indicate that reversion might occur mainly by conversion between sister chromatids. This is because the frequency of plasmid excision was about two orders of magnitude lower than the overall frequency of reversion and no reciprocal product indicative of sister chromatid exchange was found. The findings of this presentation suggest that conversion might be an important mechanism for recombination of sister chromatids and possibly for repair of damaged DNA in S or G(2).
107 citations
Journal Article•
TL;DR: Short treatments of mammalian cells with topo II inhibitors produce reversibleTopo II-mediated DNA breaks which are associated with chromosomal aberrations and SCEs whose number correlates with cytotoxicity.
Abstract: 4′-(9-Acridinylamino)methanesulfon- m -anisidide, etoposide, and 2-methyl-9-hydroxyellipticinium are antitumor topoisomerase II (topo II) inhibitors. The relationship between drug-induced sister chromatid exchanges (SCEs) or chromosomal aberrations and cytotoxicity was investigated in Chinese hamster cells sensitive (DC3F) and resistant (DC3F/9-OHE) to topo II inhibitors. Thirty-min drug treatments produced SCEs and chromosomal aberrations in sensitive (DC3F) cells, 4′-(9-acridinylamino)methanesulfon- m -anisidide being more potent than etoposide or 2-methyl-9-hydroxyellipticinium at equimolar concentrations. Comparable treatments of resistant (DC3F/9-OHE) cells did not produce chromosomal damage. The cytotoxicity of 4′-(9-Acridinylamino)-methanesulfon- m -anisidide was also greater than that of etoposide or 2-methyl-9-hydroxyellipticinium in DC3F cells, and no cytotoxicity was observed in DC3F/9-OHE at drug concentrations that produced more than two logs of cell kill in DC3F cells. A plot of cytotoxicity versus SCEs showed a good correlation between the two parameters. Therefore, short treatments of mammalian cells with topo II inhibitors produce reversible topo II-mediated DNA breaks which are associated with chromosomal aberrations and SCEs whose number correlates with cytotoxicity. In addition, topo II mutant DC3F/9-OHE cells were more sensitive than DC3F cells to the chromosomal, DNA cross-linking and cytotoxic effects of mitomycin C and were equally sensitive to the cytotoxic effect of camptothecin.
72 citations
Journal Article•
TL;DR: The distribution of alkylated deoxynucleosides and bases has been determined in the DNA of a sensitive and a resistant human glioma-derived cell line exposed to therapeutic levels of [3H]N-(2-chloroethyl)-N-nitrosourea in vitro.
Abstract: The distribution of alkylated deoxynucleosides and bases has been determined in the DNA of a sensitive and a resistant human glioma-derived cell line exposed to therapeutic levels of [3H]N-(2-chloroethyl)-N-nitrosourea in vitro The resistant cell line is 5-fold less sensitive to the cytotoxic effects of N-(2-chloroethyl)-N-nitrosourea and 8-fold less sensitive to sister chromatid exchange than the sensitive cell line In comparison with the sensitive cells, DNA from the resistant cells contains much less of the cross-link, 1-(3-deoxycytidyl),2-(1-deoxyguanosinyl)ethane DNA from the resistant cells also contains significantly fewer minor base modifications The decrease in 1-(3-deoxycytidyl),2-(1-deoxyguanosinyl)ethane cross-link formation is probably explained by the higher level of O6-alkyltransferase in the resistant cell line The lower levels of other DNA modifications could be explained by the presence of higher levels of other DNA repair activities
72 citations
TL;DR: The relative biological effectiveness (RBE) for the induction of SCE by alpha-particles in this system is undefined and effectively infinite.
Abstract: Irradiation of human G0 lymphocytes with plutonium-238 alpha-particles and X-rays was performed to investigate the production of sister chromatid exchanges (SCE). Alpha-particles produce a significant increase in SCE and this elevation is more significant when separated lymphocytes are irradiated. X-ray irradiation did not induce any significant increase in SCE. Therefore the relative biological effectiveness (RBE) for the induction of SCE by alpha-particles in this system is undefined and effectively infinite.
63 citations
Journal Article•
TL;DR: In a direct comparison, both 46BR and several Bloom's syndrome lines were found to be hypersensitive to the cytotoxic effect of simple alkylating agents, 46BR being more markedly sensitive.
Abstract: 46BR is a human fibroblast strain derived from an immunodeficient young female of stunted growth. The diploid fibroblasts as well as a Simian Virus 40-transformed cell line are hypersensitive to killing by many DNA-damaging agents, exhibit a slightly increased level of spontaneous sister chromatid exchange, and show a defect in DNA ligation in vivo . 46BR is now shown to have abnormal DNA ligase I and is similar in this regard to cell lines derived from Bloom9s syndrome patients. In a direct comparison, both 46BR and several Bloom9s syndrome lines were found to be hypersensitive to the cytotoxic effect of simple alkylating agents, 46BR being more markedly sensitive. Bloom9s syndrome lines do not exhibit the strong delay in joining of Okazaki fragments during DNA replication characteristic of 46BR. The cell line 46BR probably has a mutation in the gene encoding DNA ligase I different from those occurring in classical cases of Bloom9s syndrome.
58 citations
Journal Article•
TL;DR: The in vivo antitumor effect by CP in conjunction with caffeine appears to correlate well with the in vivo synergistic effect on cytogenetic damage caused by the combined CP plus caffeine treatment.
Abstract: Enhanced cytogenetic damage by cyclophosphamide (CP) was observed when Ehrlich ascites tumor cells were exposed in vivo to nontoxic concentrations of caffeine. One h before i.p. injection of 5-bromodeoxy-uridine adsorbed to activated charcoal Ehrlich ascites tumor-bearing mice treated i.p. with CP appear to have a dose-dependent increase in sister chromatid exchange rates and cell division delays.
Caffeine increased the survival time of the Ehrlich ascites tumor-bearing mice treated with CP and markedly reduced the ascitic volume. Therefore, the in vivo antitumor effect by CP in conjunction with caffeine appears to correlate well with the in vivo synergistic effect on cytogenetic damage caused by the combined CP plus caffeine treatment.
57 citations
TL;DR: In vivo induction of sister chromatid exchanges and micronuclei formations by acute treatment with different concentrations of sorbic acid and by nitrite gave synergistic effects which could possibly be ascribed to the formation of certain genotoxic compounds in vivo.
TL;DR: Uremia was found to increase structurally abnormal chromosomes and elevate the rate of SCE, suggesting cytogenetic changes in uremia may play a role in the heightened risk of cancer.
TL;DR: Determined DNA sequences of the germ-line regions in which the duplication of the IgG2a heavy chain constant region gene (C gamma 2a) in the murine myeloma cell line MPC-11 occurred via unequal sister chromatid exchange suggest a novel mechanism for the recombination and strongly implicates the simple sequence in the process.
Abstract: Previous studies from this laboratory have provided evidence that the duplication of the IgG2a heavy chain constant region gene (C gamma 2a) in the murine myeloma cell line MPC-11 occurred via unequal sister chromatid exchange. We now report the determination of the DNA sequences of the germ-line regions in which this exchange has occurred. The two donor sequences have long regions of virtual identity. Furthermore, both chromatids contain stretches of T-C and T-G dinucleotides; the latter has the potential to form Z-DNA. Localization of the actual breakpoints via genomic Southern blot analysis suggests a novel mechanism for the recombination and strongly implicates the simple sequence in the process.
TL;DR: Physical or preparatory as well as biological factors that modify the response and formation of SCEs make the monitoring difficult and the purpose of this article is to review and analyze these factors to facilitate an effective development of a standard protocol for SCE testing and for appropriate evaluation of test results.
Abstract: Sister chromatid exchange (SCE) reflects an interchange of DNA sequences between helices in a replicating chromosome. This was initially accomplished by Taylor and colleagues (1957) using tritiated thymidine incorporation followed by autoradiography. The development of an elegant technique for differential staining of sister chromatids by incorporating a thymidine analog, 5-bromodeoxyuridine (BrdU) has greatly simplified the detection of SCEs in metaphase chromosomes. In recent years, the analysis of SCE has been considered to be a highly sensitive and additional (i.e., with chromosome aberrations) end point for measuring mutagenic/carcinogenic potential of various environmental agents and is increasingly being used to detect and differentiate among chromosome fragility human diseases that predispose to neoplasia. Attention has been focused to see if the induction of SCEs in lymphocyte cultures can be used as a reliable "biological dosimeter" for genetic risk assessment and to monitor the exposed populations. Several physical or preparatory as well as biological factors that modify the response and formation of SCEs make the monitoring difficult. The purpose of this article is to review and analyze these factors to facilitate an effective development of a standard protocol for SCE testing and for appropriate evaluation of test results. This may also provide clues to understand the yet unknown molecular mechanism(s) and biological significance of SCE formation.
Journal Article•
TL;DR: It is suggested that long-lived lymphocytes may inefficiently repair EtO-induced lesions which produce SCE, and the results have important implications for the proper use of SCE analytical techniques in the epidemiological study of cytogenetic damage after chronic exposure to DNA-alkylating agents.
Abstract: Ethylene oxide (EtO) is a potent DNA-alkylating agent which has been shown to induce sister chromatid exchanges (SCE) in the peripheral blood lymphocytes of exposed workers. To study further the persistence of EtO-induced SCE, we have examined lymphocytes from a group of cynomolgus monkeys exposed to EtO in control, 50-ppm, and 100-ppm concentrations for 7 h/day, 5 days/week over the years 1979–1981. The data collected in 1987 were compared with those generated immediately prior to the cessation of exposure in 1981. EtO-induced SCE persisted at levels significantly above those of the nonexposed controls. Comparison of the distributions of SCE between 1979 and 1987 shows that, although mean SCE decreased from 1981 to 1987, the mean SCE in the top 10% of the distribution has not diminished over time. Consequently, the increased level of SCE is entirely attributable to a subpopulation of cells with high frequencies of SCE. These findings suggest that long-lived lymphocytes may inefficiently repair EtO-induced lesions which produce SCE. The results also have important implications for the proper use of SCE analytical techniques in the epidemiological study of cytogenetic damage after chronic exposure to DNA-alkylating agents.
TL;DR: The approach described provides an introduction to a unique means for a coordinate molecular and cytological study of dynamic changes in chromosome structure.
Abstract: Repetitive DNA sequences have been implicated in the mediation of DNA rearrangement in mammalian cells. We have tested this hypothesis by using a dihydrofolate reductase (DHFR) expression vector into which candidate sequences were inserted. DHFR- Chinese hamster ovary (CHO) cells were transfected with this vector, the amplification of which was then selected for by methotrexate (MTX) exposure. Cells transfected with the vector alone (and resistant to 0.02 or 1.0 microM MTX) or with a poly(dG-dT) insert (and resistant to 0.05 or 1.0 microM MTX) showed little change in chromosome aberrations or sister chromatid exchange frequencies. In contrast, transfection of DHFR- CHO cells with a vector containing either of two distinct 0.34-kilobase human alphoid DNA segments (and selection to 0.05 to 10.0 microM MTX) showed an approximately 50% increase in chromosome number and marked changes in chromosome structure, including one or two dicentric or ring forms per cell. The sister chromatid exchange frequency also increased, to more than double the frequency of that in cells transfected without insert or those containing poly(dG-dT). In situ hybridization of one 0.34-kilobase insert in some cells suggested clustering of homologous sequences in structurally abnormal recipient CHO cell chromosomes. The approach described provides an introduction to a unique means for a coordinate molecular and cytological study of dynamic changes in chromosome structure.
TL;DR: Smoking and coffee consumption was associated with an increase of approximately 2 SCEs per cell and a decrease in cell proliferation, and the folic acid content of cell culture medium seemed to affect neither SCE nor cell proliferation.
Abstract: Sister chromatid exchange (SCE) is a very sensitive cytogenetic assay for detecting exposure to chemical mutagens and carcinogens. One application of SCE is the monitoring of populations believed to be exposed to such agents. We have, however, relatively little knowledge about common lifestyle factors that may influence SCE and therefore complicate any study designed to examine the effects of exposure to genotoxins. In this study, we assessed the effect of cigarette smoking and coffee consumption on SCE. Smoking was associated with an increase of approximately 2 SCEs per cell and a decrease in cell proliferation. A positive linear relationship between SCE and coffee consumption was also observed. This effect was similar for smokers and nonsmokers. Additionally, the folic acid content of cell culture medium seemed to affect neither SCE nor cell proliferation.
TL;DR: A cohort study of 29 nurses who constantly handled cyto‐static drugs, and 29 controls matched according to sex and age, was carried out between 1983 and 1986, and no significant difference was observed between nurses and controls in gap, break, dicentric and translocation frequencies.
Abstract: A cohort study of 29 nurses who constantly handled cytostatic drugs, and 29 controls matched according to sex and age, was carried out between 1983 and 1986. Cytogenetic damage was assessed by sister chromatid exchanges (SCE) and chromosomal aberrations. No significant increase in mean number of SCE was found for nurses (7.37) as compared to matched controls (7.00), whereas a significant excess of SCE (p less than 0.001) was observed for smokers (8.23) as compared to non-smokers (6.75). The number of SCE was studied in relation to the amount and nature of cytostatics handled as well as to the duration of exposure. A significant association (p less than 0.05) was found between individual mean number of SCE and the total number of drugs handled after adjustment for confounding factors. In contrast, the number of SCE was not significantly related to the nature of drugs handled or to the duration of exposure. With regard to chromosomal damage, no significant difference was observed between nurses and controls in gap, break, dicentric and translocation frequencies.
TL;DR: The possibility that 4-HAA increases the frequency of SCE through some other mechanism cannot be excluded, and the increase in SCE frequency caused by 4- HAA and its analogs does not seem to be related to more general cytotoxic effects.
Abstract: Exposure of V79 Chinese hamster cells to non-cytotoxic concentrations of paracetamol (4-hydroxyacetanilide, 4-HAA) increased sister chromatid exchange (SCE) in the absence of an external activation system. Furthermore, a selective inhibition of DNA synthesis was observed at low 4-HAA concentrations. The inhibition could be counteracted by the addition of ascorbate, indicating that the effect is caused by an oxidation product of 4-HAA. In attempt to clarify possible relationships between cytotoxicity, inhibition of DNA synthesis and increased SCE, we studied the effect of 4-HAA and some related structures on these parameters. The relative position of the amino group and the hydroxyl group on the aromatic ring appear to be important for the inhibition of DNA synthesis. Removal of either of the two groups, N-acetylation and/or alkylation of the aromatic ring or phenolic oxygen decreased the effect of the aromatic amine on DNA synthesis. A significant response on SCE was observed with 4-amino-phenol, 4-HAA, 2-HAA, 3,5-dimethyl-4-HAA, 3-HAA and 2,6-dimethyl-4-HAA (none of the other compounds were tested). The increase in SCE frequency caused by 4-HAA and its analogs does not seem to be related to more general cytotoxic effects. The relative potencies of the compounds for SCE induction paralleled, for the most part, their effects on DNA synthesis. However, the induction of SCE and the inhibition of DNA synthesis did not occur at comparable concentrations. Thus, the possibility that 4-HAA increases the frequency of SCE through some other mechanism cannot be excluded.
TL;DR: A detailed study of sister chromatid exchange (SCE) in chromosomes of river buffalo reared in Southern Italy revealed non-random distribution of SCEs and possible positive relation between S CEs and heterochromatin-rich chromosome arms.
Abstract: SUMMARYA detailed study of sister chromatid exchange (SCE) in chromosomes of river buffalo (Bubalus bubalis L.) reared in Southern Italy is reported. In 34 subjects from two different farms and provinces, the total mean value of SCE/cell was found to be 8.8 ± 3.4. Of 33600 chromosomes examined, 5358 (15.9%) showed SCEs, most of which with one SCE (14.3%). An analysis of SCE-distribution on marker chromosomes (five biarmed pairs and X-chromosome) from 25 subjects, revealed non-random distribution of SCEs and possible positive relation between SCEs and heterochromatin-rich chromosome arms.
TL;DR: An in vivo drug metabolism technique is utilized for detecting the genotoxicity of indirectly acting cyclophosphamide and its directly acting metabolite phosphoramide mustard in cultures of human peripheral blood lymphocytes of normal individuals, Fanconi's anaemia and aplastic anaemia patients, wild-type Chinese hamster ovary cells (CHO) and its DNA repair-deficient mutant 43-3B cells.
Abstract: We have utilized an in vivo drug metabolism technique (i.e. injecting the chemical into rat and isolating plasma with metabolites from blood) for detecting the genotoxicity of indirectly acting cyclophosphamide and its directly acting metabolite phosphoramide mustard in cultures of human peripheral blood lymphocytes of normal individuals, Fanconi's anaemia (FA) and aplastic (AA) patients, wild-type Chinese hamster ovary cells (CHO) and its DNA repair-deficient mutant 43-3B cells. In addition, the influence of dietary carrot on the clastogenic activity of these 2 chemicals in all the different cell types was studied. The genotoxicity was assessed by the ability of the metabolites of these agents to induce sister-chromatid exchanges in the treated cells. A dose-dependent increase in the frequencies of sister-chromatid exchanges was observed in all cell strains following treatment with activated metabolites of cyclophosphamide or phosphoramide mustard. The sensitivity of lymphocytes from normal donors, FA and AA patients to these 2 chemicals was similar. In CHO cell lines the induced frequency of sister-chromatid exchanges was slightly higher after treatment with the metabolites of cyclophosphamide than with phosphoramide mustard. The mutant 43-3B cells responded with higher frequencies of SCEs when compared to the wild-type CHO cells, about 1.5–3-fold, at low doses. Pretreating of rats with fresh carrot juice effectively inhibited the increase in the frequencies of sister-chromatid exchanges induced by cyclophosphamide in wild-type and mutant CHO cells ( P p The possibility that dietary carrot exerts its antimutagenic effect by affecting the processes of enzymatic activation of cyclophosphamide is discussed.
TL;DR: It is found that 25 mg/kg of Orange G was found to be the minimum effective dose for the induction of both SCEs and chromosome aberrations in mice.
TL;DR: The activation capacity in vitro and in vivo of Vicia faba was not very pronounced, except for the activation of ethyl alcohol, when compared with that of rat-liver S9, and showed differences in activation for the 6 chemical agents tested.
Abstract: Plant activation of promutagens was studied using Vicia faba S10 (in vitro activation) and the extracts prepared from promutagen-treated roots of Vicia faba (in vivo activation). The induction of sister-chromatid exchanges in Chinese hamster ovary cells was used as an endpoint to evaluate the cytogenetic effects of promutagens activated by Vicia faba. Cyclophosphamide and ethyl alcohol were activated both by Vicia S10 and by the Vicia extracts, and their activation resulted in an increase in SCEs. Benzo[a]pyrene, 2-aminofluorene, and maleic hydrazide were not activated. Aniline was activated, but without effect on the induction of SCEs. The activation capacity in vitro and in vivo of Vicia faba was not very pronounced, except for the activation of ethyl alcohol, when compared with that of rat-liver S9, and showed differences in activation for the 6 chemical agents tested.
TL;DR: A 10- and 12-fold increase of revertant numbers could be demonstrated for 2-nitropropane (2-NP of greater than 99% purity) tested in the preincubation assay with Salmonella typhimurium strains TA 100 and TA 98 in the presence and absence of S9 mix.
Abstract: A 10- and 12-fold increase of revertant numbers could be demonstrated for 2-nitropropane (2-NP of greater than 99% purity) tested in the preincubation assay with Salmonella typhimurium strains TA 100 and TA 98 in the presence and absence of S9 mix. In the nitroreductase-deficient strains TA 100NR and TA 98NR, 2-NP was less mutagenic than in the parent strains. In human lymphocytes the induction of a weak clastogenic effect and of sister chromatid exchanges required exogenous metabolic activation. No significant mutagenic or cytogenetic response was found with 1-nitropropane of 97% purity in S. typhimurium or human lymphocytes.
TL;DR: The capacity of lesions induced by gamma radiation to produce sister chromatid exchanges (SCE) in successive divisions in mouse bone marrow cells in vivo was evaluated using a protocol for the three‐way differentiation of sister Chromatids.
Abstract: The capacity of lesions induced by gamma radiation to produce sister chromatid exchanges (SCE) in successive divisions in mouse bone marrow cells in vivo was evaluated using a protocol for the three-way differentiation of sister chromatids. Evidence was obtained that exposure to gamma radiation induces DNA lesions that result in the formation of SCE at the same locus in two successive cell divisions. The relevance of this observation with respect to DNA repair and mutagenesis is discussed.
TL;DR: Magnification, an increase in 18S + 28S ribosomal RNA genes, occurs in germ-line cells of rDNA-defecient Drosophila and resilts in a chromosomal change in rRNA gene number.
TL;DR: In a comprehensive assessment of genotoxicity, sodium fluoride was evaluated in a battery of cellular tests providing different genetic end points and biotransformation capabilities, indicating that sodium fluoride is not genotoxic in these assays.
Abstract: In a comprehensive assessment of genotoxicity, sodium fluoride was evaluated in a battery of cellular tests providing different genetic end points and biotransformation capabilities. The tests included the following: rat hepatocyte primary culture/DNA repair assay, Salmonella typhimurium histidine locus reversion assay, adult rat liver epithelial cell/hypoxanthine guanine phosphoribosyl transferase mutation assay, and sister chromatid exchange in two target cell types, human peripheral blood lymphocytes and Chinese hamster ovary cells. Negative findings were made in all assays, indicating that sodium fluoride is not genotoxic in these assays.
Journal Article•
TL;DR: Lead should be considered an agent harmful to the human chromosome after it was demonstrated that when the mean Pb-B level reached 50 micrograms/dl, the CA percentage increased significantly compared with that of the nonexposed controls.
TL;DR: In cultured human lymphocytes chlorpromazine (CPZ) was found to induce cell division delays and to have no effect on sister-chromatid exchanges (SCEs) or on mitotic indices (MIs).
Abstract: In cultured human lymphocytes chlorpromazine (CPZ) was found to induce cell division delays and to have no effect on sister-chromatid exchanges (SCEs) or on mitotic indices (MIs). CPZ induces cytotoxic effects in combination with caffeine (CAF) and alkylating agents. In combination with CAF it induced cell division delays and suppression of MIs. In combination with melphalan (MEL) and CAF, CPZ synergistically induced SCEs, caused cell division delay and suppressed MIs. In combination with chlorambucil (CBC) and CAF, CPZ produced synergism on induction of SCEs, enhanced cell division delays and reduced MIs.
TL;DR: The existence in Chinese hamster ovary cells of at least two independent functions which control resistance to methylating agents, one possibly being the capacity to repair O6-methylguanine is suggested.
Abstract: O6-Methylguanine-DNA methyltransferase (MT)-proficient Chinese hamster ovary cells were grown in the presence of low, gradually increasing levels of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) with the aim of selecting MNNG-resistant cell lines. Six resistant clones with two levels of resistance were isolated. A 3-fold increase in survival was observed in clones 13, 14 and 15 and a greater than 10-fold increase in clones A, B and C. Cross resistance to N-methyl-N-nitrosourea but not to mitomycin C was observed. By comparison with the parental MT-proficient cells, MT activity was doubled in two resistant clones (13 and B) irrespective of their resistance levels. DNA glycosylase activity responsible for the removal of 7-methylguanine and 3-methyladenine showed similar levels in resistant clones 13 and B, in the MT-proficient cells and in the original MT-deficient cells. Alkylation-induced DNA damage, as measured by alkaline elution at the same MNNG dose, was higher in clones 13 and B than in the parental cells. The induction of sister chromatid exchanges by MNNG was inversely related to the resistance levels, thus paralleling the induction of cytotoxicity. These results suggest the existence in Chinese hamster ovary cells of at least two independent functions which control resistance to methylating agents, one possibly being the capacity to repair O6-methylguanine.