Chromosome damage in rat pulmonary alveolar macrophages following ozone inhalation

To determine whether ozone is clastogenic at environmentally relevant exposure levels, rats were exposed for 6 h to 0.0, 0.12, 0.27, or 0.80 ppm ozone. The alveolar macrophages were isolated from animals sacrificed 28 h after the end of the exposure. The mitotic index and frequency of chromosome aberrations were determined. No change in the mitotic index was detected following 0.12 ppm ozone exposure. A significant decrease in mitotic index was observed after exposure to 0.27 ppm ozone; a significant (4-fold) increase in the frequency of dividing macrophages was detected following exposure to 0.8 ppm ozone. Only chromatid-type aberrations were observed. There was a significant increase in the frequency of cells with chromatid gaps and in the frequency of cells with chromatid deletions. Animals exposed to 0.27 ppm ozone had the highest proportion of cells with chromatid deletions (0.172) relative to background level (0.028). No exchanges or chromosome-type aberrations were detected in any of the animals. These data suggest that ozone, at relatively low levels, is clastogenic in macrophages from exposed rats.     

脉冲电磁场对家猪淋巴细胞的细胞遗传学效应

以家猪外周血淋巴细胞为材料,研究了脉冲电磁场（pulsing electromagnetic fields,简称PEMFS)树细胞的遗传学效应,实验发现,100和200kHz的PEMFs对家猪的淋巴细胞照射培养12,24,48h后,染色体畸变（包括非整倍体,染色体断裂等）频率明显高于对照组（P＜0．05）,其中,56％的染色体或染色单体断裂和42％的间隙发生在家猪常见染色体脆性位点部位,同时, 经100kHz和200kHz的PEMFs照射48h后,淋巴细胞姐妹染色单体交换（SCE）频率也明显高于对照组（P＜0．05）,实验结果表明,PEMFS能诱导DNA损伤和染色体畸变。     

Mutagenic activity of structurally related oxiranes and siloranes in Salmonella typhimurium

The in vitro and in vivo genotoxicity of parthenin, a sesquiterpene lactone from Parthenium hysterophorus L. with allergenic and irritant action, was assessed in three short-term tests: bacterial reversion in Salmonella typhimurium and Escherichia coli, in vitro chromosomal aberrations in peripheral blood lymphocytes and micronuclei in mouse peripheral blood. Parthenin was not mutagenic in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 but a weak response was observed in TA 102 (+S9) from 0.19 to 1.22 micromole per plate. Concentrations of 7.62 micromole per plate or higher were toxic, but the effect was reduced when S9 was present. Screening of oxidative mutagenesis with E. coli strains IC 188 and IC 203 gave negative results. Parthenin induced chromosomal aberrations, mainly chromatid breaks, in blood lymphocytes exposed to 10-60 microM during 20 h. An association was found with cytotoxicity, since concomitant nuclear alterations such as pycnosis, micronuclei and karyorrhexis were observed. Sister chromatid exchanges (SCEs) in lymphocytes were not influenced by exposure to parthenin; rather a decrease was observed at 60 microM. On the other hand, a minor increment in polyploid metaphases was found at 40 microM. When a single intraperitoneal (i.p.) dose of 4-31 mg/kg of parthenin was administered to mice, a positive increase in the micronucleated reticulocyte (RET) frequency was observed at 48 h for both sexes at the highest dose.     

Adaptive response of human lymphocytes for the repair of radon-induced chromosomal damage

In human lymphocytes low doses of X-rays can decrease the number of chromatid deletions induced by subsequent high doses of sparsely ionizing X-rays. Because of the concern with the carcinogenic effects of low doses of -particles from radon in homes, experiments were carried out to see if low doses of X-rays could also decrease the yield of chromosomal aberrations induced by subsequent exposure to radon. Human peripheral blood lymphocytes were irradiated with low doses of X-rays (2 cGy) at 48 h of culture, exposed to radon at 72 h of culture, and analyzed for the presence of chromatid aberrations at subsequent intervals. The frequency of chromatid aberrations induced by radon alone increased with time after exposure, indicating exaggerated differences in the stage sensitivity of cell cycle stages to high-LET radiation. Furthermore, the numbers of aberrations per cell did not follow a Poisson distribution but were over dispersed, as might be expected since high-LET radiations have a high relative biological effectiveness compared with low-LET radiations. Nevertheless, lymphocytes exposed to 2 cGy of X-rays before radon exposure contained approximately one-half the number of chromatid deletions compared with lymphocytes treated with radon alone and analzed at the same time. Thus, the putative chromosomal repair mechanism induced by low doses of sparsely ionizing radiation is also effective in reducing chromosomal aberrations induced by radon, which hitherto had been thought to be relatively independent of repair processes.     

Chromosomal aberrations in a fish, Channa punctata after in vivo exposure to three heavy metals

The studies were designed to assess the extent of chromosomal aberrations (CA) under the exposure of three common heavy metalic compounds, viz. mercuric chloride, arsenic trioxide and copper sulphate pentahydrate, in vivo using fish, Channa punctata (2n = 32), as a test model. Prior acclimatized fishes were divided into five groups. Group I and II served as negative and positive control, respectively. An intramuscular injection of Mitomycin-C (@ 1 mg/kg body wt.) was administered to group II only. Fishes of groups III, IV and V were subjected to sublethal concentrations (10% of 96 h LC₅₀), of HgCl₂ (0.081 mg/L), As₂O₃ (6.936 mg/L) and CuSO₄·5H₂O (0.407 mg/L). Fishes of all the groups were exposed uninterrupted for 24, 48, 72, 96 and 168 h. Observations of kidney cells of exposed fishes revealed chromatid and chromosome breaks, chromatid and chromosome gaps along with ring and di-centric chromosomes. A significant increase over negative control in the frequency of chromosomal aberrations (CA) was observed in fish exposed to Mitomycin-C, Hg(II), As(III) and Cu(II). As the average ± SE total number of CA, average number of CA per metaphase and %incidence of aberrant cells in Hg(II) was 104.40 ± 8.189, 0.347 ± 0.027 and 10.220 ± 0.842, respectively; in As(III) 109.20 ± 8.309, 0.363 ± 0.027 and 10.820 ± 2.347, respectively and in Cu(II) 89.00 ± 19.066, 0.297 ± 0.028 and 8.900 ± 0.853, respectively. Hence, it reveals that the order of induction of frequency of CA was Cu < Hg < As. The findings depict genotoxic potential of these metals even in sublethal concentrations.     

The effects of increasing dosages of X-radiation on the chromosomes of the central mudminnow, Umbra limi (Kirtland) (Salmoniformes: Umbridae)

Fish subjected to 350 R, 660 R and 990 R of X-radiation showed chromosomal aberrations such as chromatid breaks and gaps, and chromatid exchanges between several chromosomes. The frequency of aberrations/metaphase increased with radiation dosage. Likewise, the percentage of aberrant cells increased with increased irradiation. The countable metaphases fish was lower for higher doses of radiation. At lower doses single chromatid breaks accounted for most of the aberrations whereas complex aberrations involving the breakage and exchange of fragments between several chromosomes were more frequent in fish subjected to 990 R. Gill tissue yielded three times as many countable metaphases as did spleen tissue.     

Induction of genomic instability in TK6 human lymphoblasts exposed to 137Cs gamma radiation: comparison to the induction by exposure to accelerated 56Fe particles

The induction of genomic instability in TK6 human lymphoblasts by exposure to (137)Cs gamma radiation was investigated by measuring the frequency and characteristics of unstable clones isolated approximately 36 generations after exposure. Clones surviving irradiation and control clones were analyzed for 17 characteristics including chromosomal aberrations, growth defects, alterations in response to a second irradiation, and mutant frequencies at the thymidine kinase and Na(+)/K(+) ATPase loci. Putative unstable clones were defined as those that exhibited a significant alteration in one or more characteristics compared to the controls. The frequency and characteristics of the unstable clones were compared in clones exposed to (137)Cs gamma rays or (56)Fe particles. The majority of the unstable clones isolated after exposure to either gamma rays or (56)Fe particles exhibited chromosomal instability. Alterations in growth characteristics, radiation response and mutant frequencies occurred much less often than cytogenetic alterations in these unstable clones. The frequency and complexity of the unstable clones were greater after exposure to (56)Fe particles than to gamma rays. Unstable clones that survived 36 generations after exposure to gamma rays exhibited increases in the incidence of dicentric chromosomes but not of chromatid breaks, whereas unstable clones that survived 36 generations after exposure to (56)Fe particles exhibited increases in both chromatid and chromosome aberrations.     

Evaluation of malathion-induced cytogenetical effects and oxidative stress in plants using Allium test

The present study emphasized to explore the toxicity effect of malathion on plants using Allium test. The experiments explored the mitotic inhibition, growth and activity of antioxidant enzymes in roots of Allium cepa at different concentrations (50, 125, 250 and 375 ppm) of malathion under different exposure periods (3, 9 and 18 h). The results revealed that all concentrations of malathion were capable to decline the root growth. Malathion-induced mitotic alterations varying from reduction in mitotic index (MI), relative division rate (RDR) and phase distribution along with large number of chromosomal aberrations. These changes were of varying degree depending on the concentration and treatment period. The roots treated with malathion (375 ppm) showed significant (p ≤ 0.05) higher levels of superoxide dismutase and catalase than the control, while the activity of peroxidase was significantly (p ≤ 0.05) low. At 375 ppm malathion, malondialdehyde content was significantly high (p ≤ 0.05) that was increased with the treatment period. Findings concluded that variations in mitotic index, chromosomal aberrations, alterations in malondialdehyde content and activities of antioxidant enzyme could serve as the useful indicators for monitoring the effects of malathion exposures in the real scenario. Superoxide dismutase and catalase enzyme play vital roles in the antioxidant defence mechanisms under malathion toxicity. According to the data on the malondialdehyde content show malathion to be capable of producing superoxide radicals indirectly, and to result in membrane damage and oxidative stress.     

Unusual dose--response of chromosome abberrations induced in human lymphocytes by very low dose exposures to tritium

Leukocyte cultures of human peripheral blood were chronically exposed for 48 h to tritiated water and [3H]thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and [3H]thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose--response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extrapolation from the linear relation. Partial-hit or partial-target kinetic events appears at very low dose exposure.     

Increased risk of cancer in radon-exposed miners with elevated frequency of chromosomal aberrations

In spite of the extensive use of cytogenetic analysis of human peripheral blood lymphocytes in the biomonitoring of exposure to various mutagens and carcinogens, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed.In the present study, we analyzed data on 1323 cytogenetic assays and 225 subjects examined because of occupational exposures to radon (range of exposure from 1.7 to 662.3 working level month (WLM)). Seventy-five subjects were non-smokers. We found 36 cases of cancer in this cohort.Chromatid breaks were the most frequently observed type of aberrations (mean frequency 1.2 per 100 cells), which statistically significantly correlated with radon exposure (Spearman's correlation coefficient R=0.22, P<0.001). Also, the frequency of aberrant cells (median of 2.5%) correlated with radon exposure (Spearman's correlation coefficient R=0.16, P<0.02). Smoking and silicosis were not associated with results of cytogenetic analyses.The Cox regression models, which accounted for the age at time of first cytogenetic assay, radon exposure, and smoking showed strong and statistically significant associations between cancer incidence and frequency of chromatid breaks and frequency of aberrant cells, respectively. A 1% increase in the frequency of aberrant cells was paralleled by a 62% increase in risk of cancer (P<0.000). An increase in frequency of chromatid breaks by 1 per 100 cells was followed by a 99% increase in risk of cancer (P<0.000). We obtained similar results when we analyzed the incidence of lung cancer and the incidence other than lung cancer separately.Contrary to frequency of chromatid breaks and frequency of aberrant cells, the frequency of chromatid exchanges, and chromosome-type aberrations were not predictive of cancer.     

Radiation-induced chromosomal aberrations in the bone marrow of mice exposed to various doses of gamma radiation

The occurrence of chromosomal aberrations was studied at 1–14 days post-exposure in female BALB/c mice exposed to various doses of gamma radiation. The frequency of abnormal cells, chromatid and chromosome breaks, dicentrics, centric rings, acentric fragments and total aberrations increased with exposure dose, and it was highest at 7 Gy. A peak was recorded on day 1 post-exposure with a gradual decline thereafter. The chromosomal aberration yield reached a nadir on day 14 post-irradiation, without restoration to the control level. The best fit for the present data was by a linear-quadratic relationship between dose of radiation and the frequency of chromosomal aberrations.     

G2 repair and chromosomal damage in lymphocytes from workers occupationally exposed to low-level ionizing radiation

The effect of the G2 repair of chromosomal damage in lymphocytes from workers exposed to low levels of X- or gamma-rays was evaluated. Samples of peripheral blood were collected from 15 radiation workers, 20 subjects working in radiodiagnostics, and 30 healthy control donors. Chromosomal aberrations (CA) were evaluated by scoring the presence of chromatid and isochromatid breaks, dicentric and ring chromosomes in lymphocytes with/without 5 mM caffeine plus 3 mM-aminobenzamide (3-AB) treatment during G2. Our results showed that the mean value of basal aberrations in lymphocytes from exposed workers was higher than in control cells (p < 0.001). The chromosomal damage in G2, detected with caffeine plus 3-AB treatment was higher than the basal damage (untreated conditions), both in control and exposed populations (p < 0.05). In the exposed workers group, the mean value of chromosomal abnormalities in G2 was higher than in the control (p < 0.0001). No correlation was found between the frequency of chromosome type of aberrations (basal or in G2), and the absorbed dose. Nevertheless, significant correlation coefficients (p < 0.05) between absorbed dose and basal aberrations yield (r = 0.430) or in G2 (r = 0.448) were detected when chromatid breaks were included in the total aberrations yield. Under this latter condition no significant effect of age, years of employment or smoking habit on the chromosomal aberrations yield was detected. However, analysis of the relationship between basal aberrations yield and the efficiency of G2 repair mechanisms, defined as the percentage of chromosomal lesions repaired in G2, showed a significant correlation coefficient (r = -0.802; p < 0.001). These results suggest that in addition to the absorbed dose, the individual G2 repair efficiency may be another important factor affecting the chromosomal aberrations yield detected in workers exposed to low-level ionizing radiation.     

The effect of G2-treatments with 2′-deoxyadenosine on the frequency of chromatid aberrations in human lymphocytes depends on the type of culture

The effect of G₂-treatments with 2-deoxyadenosine (dAdo) on the frequency of chromatid aberrations in X-irradiated and unirradiated human lymphocytes depends on the method of culture. In whole-blood cultures dAdo alone produced very few if any aberrations, but in the presence of inhibitors of adenosine deaminase (ADA), such as EHNA or coformycin, a high frequency of chromatid gaps, chromatid breaks, and isochromatid breaks were produced. In cultures of purified lymphocytes, dAdo produced aberrations even in the absence of an ADA inhibitor. Apparently the lymphocytes are protected against the chromosome-damaging effect of dAdo by the ADA activity of the erythrocytes. — When given as a post-treatment, dAdo also enhances the frequency of chromatid aberrations induced by X-rays in G₂. In whole-blood cultures this effect is obtained even in the absence of an ADA inhibitor, although the concentration required to produce enhancement is about twenty times higher than in the presence of the inhibitor.     

Chromosome aberrations in rotogravure printing plant workers

Chromosome analysis was carried out in peripheral lymphocytes of 3 groups of workers. In 42 rotogravure printers exposed to rotogravure printing dyes and highly purified toluene at working air concentrations in the range of 104-1170 ppm (390-4380 mg/m3) for 13 years on average, an increased incidence of aberrant cells and chromatid breaks was observed. In 28 office and technical employees of the same plant, more than half of whom worked 2 h daily in the rotogravure workshop, an increased percentage of aberrant cells and chromatid breaks was also found. The difference between the 2 groups working in the printing plant and 32 controls was highly significant. The high incidence of aberrations could be explained by the exposure to toluene, but the influence of rotogravure printing dyes cannot be excluded. Smoking and high air pollution in the urban area were contributing factors in all 3 groups.     

Characteristics of γ-ray-induced chromosomal aberrations in mutagen-sensitive mutants of L5178Y cells

We have examined the chromosomal radiosensitivities of an ionizing-radiation- and MMS-sensitive mutant (M10), and a UV- and 4NQO-sensitive mutant (Q31), isolated from mouse lymphoma L5178Y cells, with regard to killing effects. In the first mitoses after 100 R γ-irradiations, it was found that M10 cells were highly radiosensitive in terms of chromosomal aberrations accompanying longer mitotic delay (3 h); the frequencies of both chromatid-type and chromosome-type aberrations were, respectively, about 7 and 4 times higher than that of wild-type L5178Y cells. Furthermore, chromatid exchanges, particularly triradials, isochromatid breaks with sister union, and chromatid gaps and breaks were markedly enhanced at G₁ phase of M10 cells. In contrast, the chromosomal radiosensitivity of Q31 cells after 100 R irradiation was similar to that of L5178Y cells. On the other hand, spontaneous aberration frequencies (overall breaks per cell) of M10 and Q31 cells were, respectively, 5.1 and 2.2 times higher than that of wild-type L5178Y cells. The chromosomal hypersensitivity to γ-rays in M10 cells is discussed in the light of knowledge obtained from ataxia telangiectasia cells.     

Cytogenetic effects of inhaled ozone in man

Peripheral blood samples were collected from 30 normal male volunteers before and at various intervals after inhaling 0.4 ppm ozone for 4 h. Data from 4 of the subjects were excluded from the analysis because of missing data points. The blood samples were cultured for 48 h, slides made and stained with a uniform Giemsa stain, and 100 metaphase spreads per subject per treatment scored for chromosome aberrations. Cells with suspected aberrations were photographed, destained, restained with a banding procedure and rephotographed to identify the specific chromosomes and regions involved.Pre-exposure, immediate post-exposure, 3 days post-exposure, 2 weeks post-exposure and 4 weeks post-exposure means for the percentage of cells with 46 chromosomes were 93.0, 93.6, 91.7, 94.5 and 94.2, respectively; in the same order, the mean number of cells with chromatid and/or chromosome breaks per 100 cells was 0.96, 0.85, 1.00, 0.88 and 0.81 respectively, and for chromatid and/or chromosome gaps per 100 cells: 1.35, 0.96, 1.35, 0.81 and 0.77, respectively. The means for each of these parameters as well as the mean frequencies of complex aberrations are not statistically significantly different between blood sampling times. The distribution of aberrations by chromosome and light and dark bands is not significantly influenced by ozone exposure.These data indicate no apparent detectable human cytogenetic effect due to exposure to ozone under the conditions of this experiment.     

In vitro genotoxic effects of ZnO nanomaterials in human peripheral lymphocytes

In this study, possible genotoxic effects of zinc oxide (ZnO) nanoparticles were investigated in cultured human peripheral lymphocytes by using chromosome aberrations and micronucleus assays (MN). For this purpose, the cells were treated with ZnO (1, 2, 5, 10, 15 and 20 μg/mL) for 24 and 48 h. In this research, four types of chromosome aberrations were observed as chromatid and chromosome breaks, fragment and dicentric chromosomes. ZnO induced significant increase of the ratio of chromosomal aberrations as well as percentage of abnormal cells at concentrations of 1, 5, 10 and 20 μg/mL in 24 h treatments. In 48 h treatments, while ZnO nanomaterials induced significant increase of the percentage of abnormal cells only at a concentration of 10 μg/mL, and of chromosome aberration per cell in comparison to the control at concentrations of 5 and 10 μg/mL. On the other hand, this material significantly increased the micronuclei frequency (MN) at concentrations of 10 and 15 μg/mL in comparison to the control. Cytokinesis-block proliferation index was not affected by ZnO treatments. It also decreased the mitotic index in all concentrations at 24 h but not at 48 h. The present results indicate that ZnO nanoparticles are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro at specific concentrations and time periods.     

Mutations and chromosomal aberrations in hMTH1-transfected and non-transfected TK6 cells after exposure to low dose rates of gamma radiation

The aim of the present study was to analyse the dose rate effect of gamma radiation at the level of mutations, chromosomal aberrations, and cell growth in TK6 cells with normal as well as reduced levels of hMTH1 protein. TK6 cells were exposed to gamma radiation at dose rates ranging from 1.4 to 30.0 mGy/h (chronic exposure) as well as 24 Gy/h (acute exposure). Cell growth, frequency of thymidine kinase mutants, and of chromosomal aberrations in painted chromosomes 2, 8, and 14 were analysed. A decline in cell growth and an increase in unstable-type chromosomal aberrations with increasing dose rate were observed in both cell lines. A dose rate effect was not seen on mutations or stable-type chromosomal aberrations in any of the two cell lines. Reduction in the hMTH1 protein does not influence the sensitivity of TK6 cells to gamma radiation. This result fits well with data of others generated with the same cell line.     

Cytogenetic effect of the anticancer drug epirubicin on Chinese hamster cell line in vitro

The present study demonstrated the cytogenetic effect of the anticancer drug epirubicin on cultures of Chinese hamster cell line in vitro. The cultures were exposed to the drug for 24 h at three final concentrations; 10, 20 and 40 microg/ml. All treatments were carried out in the absence of any exogenous metabolic activation system.The different types of structural chromosomal aberrations, including gaps, breaks, deletions and fragments were increased in epirubicin-treated cultures. This increase was dose dependent where there was a positive correlation between increased drug concentration and induction of structural chromosomal aberrations. Also, the numerical chromosomal aberrations, including hypodiploidy and hyperdiploidy, were increased significantly in epirubicin-treated cultures. Like structural aberrations, the increase of numerical chromosomal aberrations was also dose-dependent.The frequency of sister chromatid exchanges in cultures treated with epirubicin increased significantly and this increase was dose-dependent. On the other hand, the epirubicin significantly decreased the mitotic index in treated cultures of Chinese hamster cell line.     

Mentha piperita (Linn.) leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice

Oral administration of M. piperita (1 g/kg body weight/day) before exposure to gamma radiation was found to be effective in protecting against the chromosomal damage in bone marrow of Swiss albino mice. Animals exposed to 8 Gy gamma radiation showed chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges and acentric fragments. There was a significant increase in the frequency of aberrant cells at 6 hr after irradiation. Maximum aberrant cells were observed at 12 hr post-irradiation autopsy time. Further, the frequency of aberrant cells showed decline at late post-irradiation autopsy time. However, in the animals pretreated with Mentha extract, there was a significant decrease in the frequency of aberrant cells as compared to the irradiated control. Also significant increase in percentage of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges, acentric fragments, total aberrations and aberrations/damaged cell was observed at 12 hr post-irradiation autopsy time in control animals, whereas Mentha pretreated irradiated animals showed a significant decrease in percentage of such aberrations. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas Mentha pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level but the values remained below the normal. The radioprotective effect of Mentha was also demonstrated by determining the LD(50/30) values (DRF = 1.78). The results from the present study suggest that Mentha pretreatment provides protection against radiation induced chromosomal damage in bone marrow of Swiss albino mice.