Possible mutagenic action of a tularemia vaccine

No increase in the number of chromosome aberrations in the bone marrow cells of the Wistar rats was observed on the 1st, 2nd, 7th and 15th days after epidermal and intradermal immunization by tularemic live vaccine. Subcutaneous injection of great quantities of tularemic microbic cells which were not used in practice increased the number of cells with chromosome aberrations only on the second day.     

Characteristics of genomic instability in clones of TK6 human lymphoblasts surviving exposure to 56Fe ions

Genomic instability in the human lymphoblast cell line TK6 was studied in clones surviving 36 generations after exposure to accelerated 56Fe ions. Clones were assayed for 20 characteristics, including chromosome aberrations, plating efficiency, apoptosis, cell cycle distribution, response to a second irradiation, and mutant frequency at two loci. The primary effect of the 56Fe-ion exposure on the surviving clones was a significant increase in the frequency of unstable chromosome aberrations compared to the very low spontaneous frequency, along with an increase in the phenotypic complexity of the unstable clones. The radiation-induced increase in the frequency of unstable chromosome aberrations was much greater than that observed previously in clones of the related cell line, WTK1, which in comparison to the TK6 cell line expresses an increased radiation resistance, a mutant TP53 protein, and an increased frequency of spontaneous unstable chromosome aberrations. The characteristics of the unstable clones of the two cell lines also differed. Most of the TK6 clones surviving exposure to 56Fe ions showed unstable cytogenetic abnormalities, while the phenotype of the WTK1 clones was more diverse. The results underscore the importance of genotype in the characteristics of instability after radiation exposure.     

Effect of long-term exposure to thiophosphamide on the frequency of chromosome aberrations in Chinese hamster cell cultures

The paper contains the results of the study on the frequency of chromosome aberrations in the cell culture of Chinese hamster under a prolonged action of low concentrations of thiophosphamide (Thph). The frequency of chromosome aberrations in the initial period somewhat increases and then keeps to a certain constant level independently on the duration of action of thiophosphamide. With the heightening of the concentration of the chemical, a sharp increase in the number of chromosome aberrations is observed, which leads to a mass dying of the cell culture. These results may be interpreted as the action of the selection against mutant cells.     

Frequencies of chromosomal aberrations in pesticide sprayers working in plastic green houses.

The frequency of chromosome aberrations was studied in peripheral blood lymphocytes of 29 workers occupationally exposed to a mixture of pesticides and in 14 age- and sex-matched healthy controls. There was a significant increase in chromosome aberrations in sprayers when compared to unexposed persons (2.39% compared to 0.54%). No positive correlation between the frequency of chromosome aberrations and the duration of exposure was observed. No significant difference between smokers and non-smokers was found.     

The effects of beta-radiation on sister-chromatid exchanges in cultured human lymphocytes.

The incidence of Sister-Chromatid Exchanges (SCEs) due to beta-radiation was investigated in cultured human lymphocytes using the BrdU/Giemsa technique. Cultures treated continuously with 0.001 and 0.01 microCi of [3H]uridine showed no increase in either chromosome abnormalities or SCEs. Continuous treatment with 0.1 microCi resulted in a significant increase in chromosome aberrations but no increase in SCEs, while treatment with 0.2 microCi gave both an increase in chromosome aberrations and SCEs. Cultures given a 4-h pulse with 1.0 microCi showed a significant increase in both SCEs and chromosome aberrations. The results indicate that low levels of beta-radiation do not cause an increase in SCEs in human lymphocytes, and, that a number, if not all the exchanges observed at low levels of beta-radiation with autoradiography, may be spontaneous events.     

Influence of radiofrequency radiation on chromosome aberrations in CHO cells and its interaction with DNA-damaging agents

A limited number of contradictory reports have appeared in the literature about the ability of radiofrequency (rf) radiation to induce chromosome aberrations in different biological systems. The technical documentation associated with such reports is often absent or deficient. In addition, no information is available as to whether any additional genotoxic hazard would result from a simultaneous exposure of mammalian cells to rf radiation and a chemical which (by itself) induces chromosome aberrations. In the work described, we have therefore tested two hypotheses. The first is that rf radiation by itself, at power densities and exposure conditions which are higher than is consistent with accepted safety guidelines, can induce chromosome aberrations in mammalian cells. The second is that, during a simultaneous exposure to a chemical known to be genotoxic, rf radiation can affect molecules, biochemical processes, or cellular organelles, and thus result in an increase or decrease in chromosome aberrations. Mitomycin C (MMC) and Adriamycin (ADR) were selected because they act by different mechanisms, and because they might put normal cells at risk during combined-modality rf radiation (hyperthermia)-chemotherapy treatment of cancer. The studies were performed with suitable 37 degrees C and equivalent convection heating-temperature controls in a manner designed to discriminate between any thermal and possible nonthermal action. Radiofrequency exposures were conducted for 2 h under conditions resulting in measurable heating (a maximum increase of 3.2 degrees C), with pulsed-wave rf radiation at a frequency of 2450 MHz and an average net forward power of 600 W, resulting in an SAR of 33.8 W/kg. Treatments with MMC or ADR were for a total of 2.5 h and encompassed the 2-h rf radiation exposure period. The CHO cells from each of the conditions were subsequently analyzed for chromosome aberrations. In cells exposed to rf radiation alone, and where a maximum temperature of approximately 40 degrees C was achieved in the tissue culture medium, no alteration in the frequency from 37 degrees C control levels was observed. Relative to the chemical treatment with MMC alone at 37 degrees C, for two different concentrations, no alteration was observed in the extent of chromosome aberrations induced by either simultaneous rf radiation exposure or convection heating to equivalent temperatures. At the ADR concentration that was used, most of the indices of chromosome aberrations which were scored indicated a similar result.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chromosome aberrations in workers at a storage battery plant in Iraq

The present study deals with the determination of the incidence of chromosome changes in workers at a factory making storage batteries in Baghdad city. Blood samples were collected from 19 workers and 9 employees of the Scientific Research Council as control individuals, and chromosomes prepared from lymphocyte cultures were analyzed by standardized methods. Statistical analysis of the results gave significantly higher frequencies of chromatid and chromosome aberrations, particularly gaps, among the workers. No significant differences were observed in the incidence of chromosome aberrations in cells of smokers and non-smokers in both lead-exposed workers and controls. Therefore the observed increase in these aberrations was found to be associated mainly with exposure to lead oxides during the manufacture of the lead alloy grids and lead smelting.     

DNA-repair kinetics and the sensitivity of cells to X-ray-induced chromosome aberrations: a mouse myeloid leukemia cell line and normal mouse bone marrow cells

The frequency of X-ray-induced chromosome aberrations in G1 ML-1 mouse myeloid leukemia cells and normal mouse bone marrow cells increased with post-irradiation incubation with the DNA-repair resynthesis inhibitor 1-beta-D-arabinofuranosylcytosine (araC), but the frequency of aberrations in the leukemic cells increased with quite a different time response compared to the normal cells. Irradiated normal mouse bone marrow cells had a rapid increase in the frequency of chromosome exchanges and deletions with increasing araC incubation time, for example, an increase was observed with 0.5 h araC incubation. In contrast, the ML-1 cells did not have a significant increase in aberrations until 1-2 h post-irradiation incubation with araC. These results suggest that the ML-1 cells, per unit time, initially undergo less repair of the X-ray-induced DNA damage that can be converted into chromosome aberrations. We previously showed that the ML-1 cells have a higher frequency of X-ray-induced chromosome aberrations compared to normal cells and the results presented here indicate that a slower rate of repair resynthesis is contributing to the increased sensitivity of the ML-1 cells.     

Spontaneous and induced chromosome aberrations in the bone marrow cells of different strains of mice during aging

Sensitivity of bone marrow cell chromosomes to alkylating agent thiophosphamide and to gamma-irradiation has been studied in the course of ageing in 101/H, A/He, CBA, BALB/c and C57BL/6 mice. The effects of both the kinds of mutagenic treatment and of the genotype of the animals on the age-dependent changes in sensitivity of bone marrow cell chromosomes were found. Following gamma-irradiation under our experimental conditions, no variation in the output of chromosomal aberrations was observed between the strains studied. Following thiophosphamide treatment, aged mice of strains 101/H, A/He and CBA showed an increased chromosome instability as compared to young ones. In C57BL/6 mice the level of induced chromosome aberrations was found to be age-independent. Following thiophosphamide treatment, cells with multiple chromosome lesions were found in the bone marrow. The higher instability of aged animals in some strains was mainly due to a sharp increase in the number of such cells. In the intact mice of all the strains studied no age-dependent increase in the number of cells showing structural chromosome aberrations was observed, while accumulation of aneuploid cells varied with genotype.     

Studies on radiation-induced chromosome aberrations in mouse spermatocytes. I. Stage specificity and dose-response relationships of chromosome aberrations induced in mouse primary spermatocytes following X-irradiation

The cytological analysis of chromosome aberrations induced at diplotene, mid-pachytene, zygotene and leptotene stages following X-irradiation was performed at diakinesis-metaphase I in mouse spermatocytes. The dose-response relationships fitted well to linear equations for deletion-type aberrations at each stage, and to linear-quadratic equations for exchange-type aberrations at all stages except for leptotene. The radiosensitivity to chromosome aberration induction tended to increase gradually with progression through synaptic and post-synaptic stages, diplotene being the most sensitive. Chromatid exchanges were hardly observed at leptotene, the aberrations being mainly isochromatid fragments. On the contrary, chromatid exchanges and isochromatid deletions were mainly observed at later stages (zygotene-diplotene). The specificity of chromosome aberration induction in primary spermatocytes might be influenced by chromatin organization and chromosomal configuration peculiar to meiotic cells.     

Effects of vanillin on sister-chromatid exchanges and chromosome aberrations induced by mitomycin C in cultured Chinese hamster ovary cells

Effects of vanillin on the induction of sister-chromatid exchanges (SCEs) and structural chromosome aberrations by mitomycin C (MMC) were investigated in cultured Chinese hamster ovary cells. Vanillin induced neither SCEs nor chromosome aberrations by itself. However, an obvious increase in the frequency of SCEs was observed when MMC-treated cells were cultured in the presence of vanillin. The effect of vanillin was S-phase-dependent. On the contrary, the frequency of cells with chromosome aberrations was significantly decreased by the post-treatment with vanillin at G2 phase.     

The cytogenetic effect of natural mutagenesis modifiers in a human lymphocyte culture. The action of aminobenzamide during the gibberellic acid induction of chromosome aberrations

The 3-aminobenzamide sensibilization of the cytogenetic activity of gibberellic acid in the culture of human lymphocytes has been investigated. Two-three-fold increase of the chromosome aberrations induced by gibberellic acid, irrespective of the time of 3-aminobenzamide addition to the cultures (the 28th, 46th, 72th hrs of the cultivation) is shown.     

The plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene increases the mutation frequency in Chinese hamster cells]

The induction of gene mutations and chromosome aberrations by the plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene from human bladder carcinoma was studied in cultured Chinese hamster cells. Both an increase in the frequency of gene mutations to 6-mercaptopurine resistance and of chromosome aberrations was observed after pEJ6.6 treatment as compared to control series (pBR322). Thus the results of experiments carried out show that the pEJ6.6 plasmid possesses a mutagenic activity.     

Chromosome breakage in incontinentia pigmenti]

Two cases of incontinentia pigmenti in a mother and her daughter are reported. An increase in structural chromosome aberrations of the chromatid type was observed, as already described by other authors. The aberrations rate in the same individual varied from culture to culture. Chromosomal breakage was also increased in apparently healthy family members.     

Mutagenic activity of anticancer agent cis-dichlorodiammine platinum-II.

cis-Dichlorodiamminoplatinum-II (cis-DDP) has been widely used as an anticancer chemotherapeutic agent. The mutagenicity of cis-DDP was investigated in vitro and in vivo using sister-chromatid exchange analysis and the analysis of chromosomal aberrations. Parallel human lymphocyte cultures were incubated with and without the addition of BrdU at 4 concentrations of cis-DDP. Significant increases in SCE rate were observed at 0.25 micrograms/ml and higher, showing a clear dose-response relation between SCE rate and cis-DDP concentration. A significant increase in chromosome breakage and tetraradial figures was observed in BrdU free cultures treated with cis-DDP again showing a dose dependency. Analysis of the distribution of cells in the first, second and third division in cis-DDP treated cultures demonstrated the depressing effect of the drug on mitotic activity. In vivo analysis of SCE and chromosome aberrations in mouse showed that 13.85 mg/kg i.p. of cis-DDP produces significant increases in the rate of SCE and chromosome aberrations in bone-marrow cells.     

Chromosome damage induced in human lymphocytes by 5-methoxypsoralen and 8-methoxypsoralen plus UV-A

The induction of structural chromosome aberrations and sister chromatid exchanges (SCE) was studied in human lymphocytes in vitro after treatment with the two bifunctional furocoumarins 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) in the presence of UV-A. The results show that both psoralens induce a dose-dependent increase in the SCE rate as well as in structural chromosome aberrations. 5-MOP was 2.0-2.5 times more effective for the induction of chromosome breaks and had a slightly stronger effect with respect to SCE induction. A significant influence on proliferation kinetics could be observed only with 5-MOP plus UV-A.     

Long-Term Monitoring of Cytogenetic Aberrations in Adolescents of a Large Industrial Town

Long-term cytogenetic monitoring was carried out in adolescents of the town of Kemerovo. In total, aberrant metaphase frequency increased from 1.53% in 1992 to 4.40% in 1996 in Kemerovo adolescents, being significantly higher than a control frequency from 1993 to 1996. In all samples, chromosome aberrations mostly included acentric fragments, while exchanges were rare. The highest number of aberrations per aberrant metaphase was 2 in Kemerovo adolescents and 1 in the control sample. The observed increase in total number of chromosome aberrations suggests that the mutagenic effect of chemical environmental pollutants on Kemerovo adolescents increased over the five years.     

Genotoxic effects of malathion: an organophosphorus insecticide, using three mammalian bioassays in vivo

The genotoxic effects of malathion was evaluated using chromosome aberration, sister chromatid exchange (SCE) and sperm abnormality assays in mice. All the three acute doses (2.5, 5 and 10mg/kg) of malathion tested in the present study, induced significant dose-dependent increase in the frequency of chromosome aberrations and sperm abnormalities, but did not affect the total sperm count. The highest acute dose induced a >12-fold increase in the frequency of chromosome aberrations, two-fold increase in the frequency of SCEs and four-fold increase in the frequency of sperms with abnormal head morphology following intraperitoneal (i.p.) exposure. Further, a significant increase in the frequency of SCEs was observed, but the increase was not dose-dependent. At higher doses, malathion induced a moderate delay in cell cycle as evident from the increase in average generation time (AGT). The present findings suggest that technical grade malathion is a potent genotoxic agent and may be regarded as a potential germ cell mutagen also.     

The effect of a Coxsackie viral infection on the chromosomal apparatus of the cells of fetuses and newborn mice]

The Coxsackie virus B1 has been studied for its effect on the chromosome apparatus in cells of mouse feti and newborn mice in case of intraperitoneal infection of females on the 3d week of pregnancy. It is stated that the virus readily moves across the placental barrier and induces chromosome aberrations in the cells of feti, their number being 2.5 times higher than the control level. The maximal number of structural chromosome aberrations was registered during the first three days from the moment of infecting. Then a gradual decrease in the number of aberrant metaphases in the cells of newborn mice was observed. It had reached the value of the control level by the 17th day of observation.     

Multiyear dynamics of cytogenetic abnormalities in adolescents from a large industrial city

Long-term cytogenetic monitoring was carried out in adolescents of the town of Kemerovo. In total, aberrant metaphase frequency increased from 1.53% in 1992 to 4.40% in 1996 in Kemerovo adolescents, being significantly higher than a control frequency from 1993 to 1996. In all samples, chromosome aberrations mostly included acentric fragments, while exchanges were rare. The highest number of aberrations per aberrant metaphase was 2 in Kemerovo adolescents and 1 in the control sample. The observed increase in total number of chromosome aberrations suggests that the mutagenic effect of chemical environmental pollutants on Kemerovo adolescents increased over the five years.