Increase In Frequency Of Chromosomal Aberrations Research Articles

The in vitro cytotoxic, genotoxic, and oxidative damage potentials of the oral artificial sweetener aspartame on cultured human blood cells

Background/aimAspartame (APM, L-aspartyl-L-phenylalanine methylester) is a low-calorie, nonsaccharide artificial sweetener widely used in foods and beverages. When metabolized by the body, APM is broken down into aspartic acid, phenylalanine amino acids, and a third substance, methanol. Since the amino acid phenylalanine serves as a neurotransmitter building block affecting the brain, and methanol is converted into toxic formaldehyde, APM has deleterious effects on the body and brain. Thus, its safety and, toxicity have been the subjects of concern ever since it was first discovered. Although many studies have been performed on it, due to the presence of conflicting data in the literature, there are still numerous question marks concerning APM. Therefore, the safety of aspartame was tested using in vitro methods.Materials and methodsWe aimed to evaluate the in vitro cytotoxic effects by using 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase release tests, genotoxic damage potential by using chromosome aberration (CA) assay, and antioxidant/oxidant activity by using total antioxidant capacity (TAC) and total oxidative stress (TOS) analysis in primary human whole blood cell cultures.ResultsThe results of the MTT test showed that APM led to significant decreases in cell viability in a clear concentration-dependent manner. Moreover, an increase in CA frequency was found in the cells treated with APM. However, APM treatments did not cause any significant changes in TAC and TOS levels in whole blood cultures.ConclusionOverall, the obtained results showed that APM had genotoxicity potential and a concentration-dependent cytotoxic activity in human blood cells.

Assessment of anilofos-induced mutagenicity in bone marrow and germ cells of Swiss albino mice.

Anilofos is an organophosphate compound and is used extensively as a preemergence and early postemergence herbicide for the management of sedges, annual grasses, and some broad-leaved weeds in rice fields. The present study was aimed to assess the mutagenic potential of anilofos after sub-chronic exposure in Swiss albino mice. For this, a combined approach employing micronucleus (MN), chromosomal aberration (CA) studies and sperm-head abnormalities (SHAs) was used. Three dose levels of 1%, 2%, and 4% of maximum tolerated dose (MTD) (235 mg/kg b.wt.), that is, 2.35, 4.7 and 9.4 mg/kg b.wt., respectively, were administered orally daily for 90 days. A higher incidence of micronucleated erythrocytes (polychromatic erythrocytes + normochromatic erythrocytes), significant increase in CA frequency, and significant decrease in the ratio of polychromatic/normochromatic erythrocytes (P/N) ratio were observed at the 4.7 and 9.4 mg/kg b.wt. dose levels. A significant increase in SHA was observed in all treatment groups (2.35, 4.7, and 9.4 mg/kg b.wt.) from the control group. In conclusion, anilofos exposure of 2% and 4% of MTD caused a higher rate of micronucleated erythrocytes, increased frequency of CA, increase in SHA, and lower P/N ratio, and pesticide exposure of 1% of MTD only resulted in higher SHAs. Thus, anilofos was found to have mutagenic potential in mice when administered daily orally at dose rate of 4.7 and 9.4 mg/kg b.wt. for 90 days.

Occupational and life-style factors-acquired mutagenicity in agric-workers of northeastern Brazil.

Pesticides are a complex mixture of chemicals used to protect crops from a number of pests and diseases. They have been considered as potential mutagenic agents. This study aims at evaluation of the mutagenic effect of pesticide exposure to agricultural workers through chromosomal aberrations (CA) and micronucleus (MN) assay in peripheral blood lymphocytes and oral mucosal cells, respectively. The exposed group was consisted with 97 farmers, while the control (un-exposed) group consisted of 55. The results showed a significant (p<0.05) increase in frequency of CA and MN in the exposed group. Both CA and MN profiles were linked to a significant (p<0.05) co-relation with the confounding factors such as smoking habits, alcohol, vegetables, tea/coffee, vitamins, and sweetener consumptions. More cytogenetic events were denoted in smoking and alcohol consumption as well as non-personal protective equipment (non-PPE) and low/no vegetables user farmers. In conclusion, a deficiency of dietary and medicaments-derived antioxidants, while consumption of alcohol and tobacco, as well as effects of radiation, heavy metal poisoning (especially from sweeteners), and non-PPE using habits, may contribute cytogenetic damage to the workers.

Assessment of dose and DNA damages in individuals exposed to low dose and low dose rate ionizing radiations during computed tomography imaging

PurposeComputed tomography (CT) is a frequently used imaging modality that contributes to a tenfold increase in radiation exposure to the public when compared to other medical imaging modalities. The use of radiation for therapeutic need is always rationalized on the basis of risk versus benefit thereby increasing concerns on the dose received by patients undergoing CT imaging. Therefore, it was of interest to us to investigate the effects of low dose and low dose-rate X-irradiation in patients who underwent CT imaging by recording the doses received by the eye, forehead and thyroid, and to study the levels of damages in the lymphocytes in vivo. Materials and methodsLithium manganese borate doped with terbium (LMB:Tb) thermo luminescence dosimeters (TLD) were used to record the doses in the patient’s (n=27) eye, forehead, and thyroid and compared with the dose length product (DLP) values. The in vivo DNA damages measured were compared before and after CT imaging using chromosomal aberration (CA) and micronucleus (MN) assays. ResultsThe overall measured organ dose ranged between 2±0.29 and 520±41.63mGy for the eye, 0.84±0.29 and 210±20.50mGy for the forehead, and 1.79±0.43 and 185±0.70mGy for the thyroid. The in vivo damages measured from the blood lymphocytes of the subjects showed an extremely significant (p<0.0001) increase in CA frequency and significant (p<0.001) increase in MN frequency after exposure, compared to before exposure. ConclusionThe results suggest that CT imaging delivers a considerable amount of radiation dose to the eye, forehead, and thyroid, and the observed increase in the CA and MN frequencies show low dose radiation effects calling for protective regulatory measures to increase patient’s safety. This study is the first attempt to indicate the trend of doses received by the patient’s eye, forehead and thyroid and measured directly in contrast to earlier values obtained by extrapolation from phantoms, and to assess the in vivo low dose effects in an Indian patient population undergoing CT procedures.

Apoptosis , Cytogenetic and Endothelial Progenitor Cells in the Peripheral Blood of Industrial Radiographers

Background: Radioactive sources and fixed or mobile X-ray equipment are used for both process and quality control in the metallurgical and fertilizer industries. Workers in the nuclear industry are a suitable sector of the populace for the direct estimation of radiation effects at low doses as they are typically monitored and restricted to effective doses of 100 mSv every 5 years. A dose-related increased mortality from circulatory diseases has been observed in some studies of nuclear industry workers, but it is unclear whether this reflects a real effect of radiation exposure or a spurious one. The aim of the present study was to detect the circulating endothelial progenitor cells (EPCs) in the peripheral blood and the frequency of micronuclei (FMN) among industrial radiographers occupationally exposed to ionizing radiation at the Steamer’s Welding Company and EL Nasr Company for the manufacture of Fertilizers and Chemicals in Suez and Talkha, Egypt. Material and Methods: Venous blood samples were obtained from 30 industrial radiographers exposed to x-rays during industrial procedures vs. 20 persons not exposed to ionizing radiation as control subjects. Blood samples were assayed for total and differential blood counts and cell phenotype of circulating EPCs, whose surface markers were identified as CD34, CD133 and kinase domain receptor (KDR), frequency of chromosomal aberrations (FCA), apoptosis percentage in circulating lymphocytes together with plasma stromal cell derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF). Results: The results of this study revealed a significant increase in FCA with respect to total number of dicentrics (0.09 ± 0.03 vs. 0.0005 ± 0.0001) and rings (0.01 ± 0.0012 vs. 0) together with apoptosis percentage (7.3 ± 2.8 % vs. 2.4 ± 1.5 %) among industrial radiographers compared to control subjects respectively, indicating radiation exposure among such workers. Also a significant increase was observed in plasma SDF-1α (2750 ± 370 vs. 2270 ± 430pg/ml), VEGF (157.9 ± 16.9 vs. 137.5 ± 12.6 pg/ml) among industrial radiographers compared to control subjects. Percentage of circulating mononuclear cells expressing CD34 (53 ± 3.9 vs. 54.2 ± 10.6/ 105 mononuclear cells), CD133 (82.4 ± 4.8 vs. 54.2 ± 10.6/ 105 mononuclear cells) and KDR (48.7 ± 12.5 vs. 43.5 ± 8.2/ 105 mononuclear cells) was significantly higher among industrial radiographers compared to control subjects. Conclusion: It is concluded that the industrial radiographers have increased numbers of circulating EPCs and increased levels of SDF-1 and VEGF, which denotes an increased capacity for tissue repair.

Diabetes--increased risk for cancers through chromosomal aberrations?

Diabetes, a comprehensive genetic disease, is principally due to the deregulation of glucose levels in the blood. In addition to contemporary epidemiological studies, systematic substantiation suggests that long-term diabetes leads to cancers due to a variety of reasons. In this study, blood samples were collected with informed consent from confirmed type I diabetic (T1DM, n=25) and type II Diabetic patients (T2DM, n=25) with equal numbers of controls. Further depending on the lifestyle habits they were subdivided into smokers/non-smokers and alcoholics/non-alcoholics. Chromosomal assays were performed for these cases and it was found that there was a significant increase in chromosomal aberration frequency in diabetic patient groups who are exposed to smoking and alcohol than that of normal diabetic groups (T1DM and T2DM). On the other hand, patient groups who were non-smoking and non-alcoholics also showed higher chromosomal aberrations when compared to that of controls. While the mechanisms for these increased chromosomal aberrations in diabetic groups are not clear, they may be due to increased oxidative stress leading to oxidative damage and resulting in genomic instability, which in turn may contribute to an increased risk for cancer.

Cytotoxic and genotoxic effects of sodium hypochlorite on human peripheral lymphocytes in vitro

Chlorination is widely used method in the disinfection of drinking and utility water worldwide. In this study, cytotoxic and genotoxic effects of sodium hypochlorite were investigated by the cytokinesis-block micronucleus assay and chromosomal aberration analysis on human peripheral lymphocytes in vitro. A significant increase in chromosomal aberration frequency was observed in all treatments of NaOCl (0.030, 0.065, 0.100, 0.25, 0.5, 1, 2, 4 mug/mL) at 24 and 48 h compared with the negative control and mitomycin C (MMC, 0.3 mug/mL), which was used as a positive control. NaOCl significantly increased the frequency of micronuclei in a dose dependent manner. The results showed that there was a significant correlation between NaOCl concentration and chromosomal aberration, micronuclei frequency, necrotic cells, apoptotic cells and binucleated cells.

Induction of chromosome aberrations in cultured human lymphocytes treated with sand dust storm fine particles (PM2.5)

The clastogenic activity of airborne air fine particulate matter (PM2.5, particulates with an aerodynamic diameter ≤2.5 μm) has already been demonstrated. However little is known about the health risks associated with sand dust storm PM2.5 and its extract. In order to investigate the clastogenic activity of sand dust storm PM2.5 (include its organic and inorganic extract) on human lymphocytes, the normal PM2.5 and sand dust storm PM2.5 samples were collected in Wuwei city (Gansu Province) and Baotou city (Inner Mongolia), China. The chromosomal aberration (CA) test was employed and the cells were treated with 0, 33, 100, 300 μg ml −1 sand dust storm or normal ambient air PM2.5 suspension (physiological saline as solvent control), or inorganic extract (0, 75, 150, 300 μg ml −1, physiological saline as solvent control) or organic extract (0, 20, 40, 80 μg ml −1, DMSO as solvent control) at the beginning of the cell culture. The results indicated that sand dust storm PM2.5 and its extract as well as normal samples can induce increase in CA frequency. With the increase of treatment concentrations the CA frequency increased and the mitotic index (MI) values declined in a dose–response manner. In the same concentrates, the CA frequency of normal ambient air PM2.5 and its extract were significant higher than those of sand dust storm PM2.5 ( P < 0.05 or 0.01) except the treatment of Wuwei sample at higher doses (100, 300 μg ml −1), the treatment of inorganic extract of PM2.5 at the highest dose (300 μg ml −1) and the treatment of organic extract of PM2.5 at the higher dose (40 and 80 μg ml −1) either in Baotou or in Wuwei ( P > 0.05). The toxicity of sand dust storm PM2.5 and its extract at high dose is very potent. CA frequency of normal PM2.5 (include its organic extract) from Baotou were higher than those of Wuwei especially in low and middle dose ( P < 0.05), but the treatment results of sand dust storm PM2.5 (include its all extract) was not significant different between the cities ( P > 0.05).

Early induction of genetic instability and apoptosis by arsenic in cultured Chinese hamster cells.

In order to assess at what time from the beginning of exposure inorganic arsenic can give rise to genetic instability and trigger apoptosis, V79-C13 Chinese hamster cells were treated with 10 microM sodium arsenite for 24 h. Under these conditions, cell survival was >70% and cells showed neither an increase in chromosome aberration frequency nor a delay in cell cycle progression. Investigations, which were carried out every 6 h during the treatment, revealed an early appearance of genetically unstable cells, namely micronucleated, multinucleated and mononucleated 'giant' cells, as well as apoptotic cells. Indirect immunostaining using anti-beta-tubulin antibody showed severe alterations in spindle morphology after only 6 h treatment, when cells with small spindles whose poles were inside the metaphase plate appeared, and after 12 h treatment, when cells in which spindle assembly had completely failed were observed. These cells, unable to complete mitosis, underwent apoptosis. In fact, cells which turned out to be positive in the TdT-FragEL test had condensed chromatin arranged in metaphase-like plates; their maximum frequency was reached after 24 h treatment. A cytogenetic study was conducted at the end of the period of exposure to arsenic and after post-treatment incubation in fresh medium for up to 5 days. It showed that the percentage of cells with 21 chromosomes (modal number of the cell line) decreased, making way for aneuploid cells. Arsenic, therefore, induced early genetic instability or apoptosis in dividing cells. However, while apoptosis tended to cease when arsenic was removed from the culture medium, the acquired instability remained and propagated within the cell population.

Cytogenetic study of chronic ethanol consumption in rats.

Ethanol was supplied in the drinking water of Wistar rats at a concentration of 20% v/v for up to 30 days. The animals treated with ethanol demonstrated a nonsignificant increase in chromosomal aberration frequency when compared with control animals. The mitotic index values obtained indicated no significant differences between ethanol treatment and control groups. The final weights of control rats were significantly greater than those of the ethanol-treated group. Chronic administration of ethanol showed no clastogenic or cytotoxic effect. After chronic ethanol consumption, the cytochromes P450 activity increases, thus possibly preventing the ethanol that has entered the circulation from reaching excessive levels, leading to metabolic adaptation and/or tolerance.

Cytogenetic effects of 50 Hz magnetic fields of different magnetic flux densities

Cytogenetic investigations were performed in human peripheral blood lymphocytes following exposure to 50 Hz magnetic fields alone or in combination with the chemical mutagen mitomycin C or with X-rays. It was found that magnetic fields up to 2500 μT did not significantly influence the chromosome aberration and sister chromatid exchange frequency. Also, the combined treatments failed to indicate the presence of any synergistic, potentiating, or antagonistic effect between the ELF magnetic fields and the mutagens. However, there were two exceptions: Cells exposed to 504 μT magnetic fields before and during cultivation displayed a statistically significant decrease in sister chromatid exchange frequency. Also, when cells were cultivated in the presence of 88.4 μT magnetic fields following X-ray exposures there was a significant increase in chromosome aberration frequency compared to X-ray exposure alone. Bioelectromagnetics 21:589–596, 2000. © 2000 Wiley-Liss, Inc.

Cytogenetic effects of 50 Hz magnetic fields of different magnetic flux densities

Cytogenetic investigations were performed in human peripheral blood lymphocytes following exposure to 50 Hz magnetic fields alone or in combination with the chemical mutagen mitomycin C or with X-rays. It was found that magnetic fields up to 2500 microT did not significantly influence the chromosome aberration and sister chromatid exchange frequency. Also, the combined treatments failed to indicate the presence of any synergistic, potentiating, or antagonistic effect between the ELF magnetic fields and the mutagens. However, there were two exceptions: Cells exposed to 504 microT magnetic fields before and during cultivation displayed a statistically significant decrease in sister chromatid exchange frequency. Also, when cells were cultivated in the presence of 88.4 microT magnetic fields following X-ray exposures there was a significant increase in chromosome aberration frequency compared to X-ray exposure alone.

Radiation-induced chromosomal aberrations and haematological alterations in hospital workers.

Long-term exposure to low doses of ionizing radiation may affect cells and tissues and result in various adverse health effects. The purpose of this study was to investigate whether chromosome aberrations and haematological alterations could be used as biomarkers of possible radiation injury in workers exposed to ionizing radiation. Groups totalling 323 medical professionals handling X-ray equipment and 160 control subjects were examined for incidence of chromosome aberrations and changes in leukocyte, lymphocyte and thrombocyte counts. The incidence of all types of chromosome aberrations was higher in the exposed groups than in controls, yet no significant difference was found between the exposed groups. A many-fold increase in chromosome aberration frequency in all exposed groups was not followed by a corresponding haematological depression. This suggests that chromosome aberrations are a significantly more sensitive indicator of changes caused by low doses of ionizing radiation than haematological alterations.

The influence of temperature on chromosome aberrations in tissue culture: Relation to thermal aging

Chromosome aberrations were scored in V-79 strain Chinese hamster cells grown in vitro. The percent of aberrant mitoses observed in anaphase and early telophase increased significantly with temperature over the range of values between 35° and 40°C. No significant increase in aberration percentage was observed when the culture growth time was extended from 2 to 3 days. The progressive increase in chromosome damage with temperature supports the concept that genetic information is thermally degraded even at temperatures in the normal physiological range. Since an increase in chromosome aberration frequency is correlated with aging, it may be that thermally induced information loss is an important factor in the aging process. However, the dependence of the aberration percentage on temperature is not sufficiently strong to fully explain the thermal loss of proliferative capacity of cells in culture. Additional temperature-dependent processes must occur and may further contribute to the thermal destruction of cellular information.

Radiation Sensitivity of Tradescantia Microspore Chromosomes to a Second Exposure of X-Rays

Tradescantia microspores were irradiated with 400 r of x rays and 2 days later with 50, 70, or 100 r. The cells were fixed and stained 23 to 27 hours after the second exposure. The first exposure produced only chromosome aberrations, and the second exposure produced only chromatid aberrations. The frequency of cells with chromatid aberrations in the cells which had been subjected to 400 r of x rays was much higher than in cells which had received only 50, 70, or 100 r, indicating that the irradiation of the cells at the resting stage made the chromosomes more sensitive to irradiation at prophsse. Irradiation at the early resting stage resulted in some increase in chromosome aberration frequency by the second dose given at the late resting stage, but the results are of doubtful statistical significance. An analysis of microspores which had been given 400 r followed by 50, 70, or 100 r shows that the cells with no chromosome aberrations induced at the resting stage were twice as sensitive to irradiation at prophase as the cells which contained one or more chromosome aberrations which had been induced at the resting stage, and microspores with only one chromosome aberration weremore » more sensitive to irradiation at prophase than microspores with two chromosome aberrations, although all cells had been subjected to 400 r of x rays at the resting stsge. (auth)« less