Different Types Of Chromosomal Aberrations Research Articles

Mitotic chromosomal abnormalities and DNA polymorphism in the Nile tilapia (Oreochromis niloticus, Linnaeus, 1758) as a biomarker for water pollution by heavy metals.

Mitotic chromosomal aberrations and DNA polymorphism (RAPD marker) were carried out on the Nile tilapia Oreochromis niloticus collected from five sites in Minia governorate, Egypt to test their applicability as biomonitors for heavy metal contaminants of water. The diploid chromosome number of O. niloticus population was 2 n=44. Different types of chromosomal aberrations were recorded (e.g., deletion, ring, centromeric attenuation, end-to-end association, dicentric chromosome, stickiness chromosomes, endomitosis, fragments and chromatid gap). The chromosomal aberrations varied between O. niloticus population collected from five sites, and the most common type was ring (R) chromosomes. Samples obtained from Bahr Yousef and Irrigation drain exhibited the highest aberration frequency. The frequency of chromosomal aberration was positively correlated with the concentration of heavy metals where their concentration in the surface water of Irrigation drain and Bahr Yousef exceeded the limits defined by WHO as well as the concentration of Pb in muscles. The RAPD marker was also used to identify genetic variation among Nile tilapia samples collected from five different water sources. It created polymorphic and unique bands that can be used as genetic markers to track DNA variations. The dendrogram also revealed that exposure to heavy metal pollution causes gradual accumulation of variance, whereas areas subjected to environmental stress showed higher genetic variation and clustered together.

Alpha-Particle Exposure Induces Mainly Unstable Complex Chromosome Aberrations which do not Contribute to Radiation-Associated Cytogenetic Risk.

The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0-6 Gy X rays or 0-2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.

Detailed Classification of Chromosome Aberrations with Undifferentiated Staining to Account for Clastogenic Effects of Radionuclide and Complex Contaminations

Examples of the use of different types of chromosome aberrations as diagnostic indicators to solve the practical problems of radioecology were considered. The classifications of the chromosome aberrations used to estimate the clastogenic effect of factors of radiation and chemical nature according to the results of cytogenetic studies with uniform staining of the chromosomes were analyzed. Some terminological inconsistency and ambiguity when designating various types and categories of chromosome aberrations, reflecting the clastogenic effect, was detected. It was demonstrated that this inconsistency can complicate the use of such cytogenetic indices in radioecological practice. According to the results of the Allium test using a digital imaging system, original microimages demonstrating the configurations of aberrant chromosomes used in classifications were obtained.

Полногеномное ассоциативное исследование связи полиморфных локусов с повышенной частотой хромосомных аберраций у лиц, подвергавшихся длительному радиационному воздействию

Purpose: To conduct genome wide association study of the association of 750,000 SNPs and an increased frequency of different types of chromosomal aberrations, induced by chronic irradiation in the dose range of 100–300 mSv.
 Material and methods: The study was conducted among Siberian Group of Chemical Enterprises healthy employees (n = 37) exposed to professional external γ-radiation in a dose range of 100–300 mSv. The de novo induced CNVs were previously detected in these persons. Mean dose – 188.8 ± 8.3 mSv, median – 185 mSv, interquartile range – 147.8–218.7 mSv, min – 103.4 mSv, max – 295.8 mSv. Genotyping of DNA samples from 37 employees was carried out by microarray CytoScan™ HD Array (Affymetrix, USA), containing 750,000 SNP-markers of 36,000 genes. The standard cytogenetic analysis was performed in the entire examined group.
 Results: We analyzed the association of these SNPs with the frequencies of aberrant cells and following chromosomal aberrations: single chromatid fragments, chromatid exchanges, paired fragments, dicentrics, rings, and translocations. We have found that 8 SNPs (rs10779468, rs158735, rs158710, rs158712, rs11131536, rs528170, rs9533572, rs10512439) are associated with the frequency of aberrant cells.
 Conclusion: We have discovered polymorphic variants that are associated with an increased frequency of aberrant cells in workers of Siberian Group of Chemical Enterprises exposed to irradiation at a dose of 100–300 mSv. This polymorphic variants can be considered as potential markers of individual radiosensitivity. To confirm identified associations, further validation studies on an extended sample of people exposed to radiation are needed.

The impact of several hydraulic fracking chemicals on Nile tilapia and evaluation of the protective effects of Spirulina platensis.

Hydraulic fracturing (fracking) chemicals are used to maximize the extraction of hard-to-reach underground energy resources. Large amounts of fracking fluid could escape to the surrounding environments, including underground and surface water resources, during the chemical mixing stage of the hydraulic fracturing water cycle due to equipment failure or human error. However, the impact of pollution resulting from operational discharges is difficult to assess in aquatic ecosystems. In this study, pathological investigations, chromosomal aberrations, DNA damage, and biochemical and hematological parameters were used to evaluate the effects of such chemicals on Nile tilapia. Chromosomal aberrations are considered very sensitive genetic markers of exposure to genotoxic chemicals and are used as indicators of DNA damage. The appearance of different types of chromosomal aberrations (gaps and breaks) due to chemical exposure was significantly reduced by treatment with spirulina. Various deleterious findings in Nile tilapia, in the current study, could attributed to the presence of fracking chemicals in the aquatic environment. However, the presence of spirulina in the diet reduced the hazards of such chemicals. In addition, cytogenetic studies in the current work revealed the importance of spirulina in ameliorating the genotoxic effects of a mixture of some chemicals used in fracking.

The Effect of Waterpipe Smoking on DNA Integrity Among Youth in Jordan

Waterpipes have been used to smoke tobacco and other substances by the indigenous people of Africa and Asia for at least four centuries. Waterpipe smoking causes different genotoxic effects. The evaluation of chromosome aberrations (CAs) is one of the standard methods used for assessing the DNA damage in human subjects. The aim of this study was to determine whether waterpipe smoking increases the frequency of different types of CAs in the peripheral blood lymphocytes of young waterpipe smokers ( $$n=25$$ ) compared with non-smokers ( $$n=25$$ ) in Jordan. Twenty-five metaphases were scored and evaluated for chromosome breakage, fragment and gap for each individual. Chromosomal breakage ratios were detected to be $$2.53\pm 1$$ and $$0.576\pm 0.64$$ in the waterpipe smokers and non-smokers groups, respectively. The fragments ratios were $$2.19\pm 0.9$$ and $$0.72 \pm 0.05$$ , and the gaps ratios were $$2.15\pm 0.67$$ and $$0.6\pm 0.5$$ in the waterpipe smokers and non-smokers groups ( $$p <0.0001$$ ), respectively. The results of the study revealed a significant increase in the frequencies of different types of CAs in waterpipe smokers compered to non-smokers, suggesting that smoking a waterpipe may cause genotoxic effects.

Features of the state of the chromosomal apparatus of spouses with disorders of reproductive function

Chromosomal anomalies are the most frequent reason of infertility in the world. This is one of the reasons for abortion in the early stages, stillbirth or the birth of a child with multiple malformations. The general level of chromosomal aberrations in the population is 0.5-3.0 %, while among people with impaired fertility this level ranges from 2.9 to 14%. The results of karyotyping of 1024 patients with problems of reproduction function, which appealed to the Center of Human Reproduction «Clinic of Professor Feskov O.» in the period from 2009 to 2014, were presented in the article. For the cytogenetic research of patients, metaphase chromosomes were used. Samples were obtained from culture of peripheral blood according to standard technique. For staining of chromosomes slides GTG-method and CBG-method were used. Analysis of slides was carried out in accordance with the International system of the cytogenetic nomenclature. Different types of chromosomal aberrations have been detected in the karyotypes of the patients in 6.05% cases, in population this value is 0.5–3.0 %. This increase in the number of changes in karyotype in patients with infertility in comparison with the population level is statistically significant (р˂0.05). There are numerical chromosome abnormalities, structural chromosome rearrangements and chromosomes polymorphisms in the patients. Among identified changes the chromosomes polymorphisms are more frequent, it total 2.4% in our group. Among them 1.25% cases of increase in length of satellite on the short arm of acrocentric chromosomes, 0.67% – increase in length of centromeric heterochromatin, 0.38% – increase in length of heterochromatin on the long arm of chromosomes 9, 16, Y. Structural chromosome rearrangements were found in 2.11% patients, among them inversions – 0.86%, Robertsonian translocations and reciprocal translocations – 0.58% і 0.1% respectively, insertions – 0.1%, additional material of unknown origin – 0.1% and marker chromosomes – 0.1%. Numerical chromosomes abnormalities have been detected in 1.63% cases (17 patients out of 1042) – among them Klinefelter syndrome – 0.67% patients, and cases with different mosaic karyotype for sex chromosomes – 0.96%. So it is recommended to carry out karyotyping of couples with infertility.

Genotoxic effects of Peganum harmala L. in relation to traditional use

Peganum harmala L. is a well-known medicinal plant, widely distributed and used in folk medicine. Recently, numerous reports have been published regarding the pharmacological and therapeutic effects of P. harmala and its major alkaloids components. However, mammalian toxicity due to P. harmala alkaloids extract has been rarely investigated. The present research aimed to study the genotoxic effects of harmala plant extract in relation to traditional use. Harmala crude alkaloid was extracted and the toxicity of the extract was examined on albino mice by intraperitoneal injection. The genotoxic effects of the alkaloid extract was tested on bone marrow cells isolated from sacrificed mice. The total seeds alkaloids showed moderate toxic effects on male albino mice with LD50 350 mg/ Kg body weight. P. harmala alkaloids extract showed significant reduction in the mitotic index (MI) and increased depression of mammalian cells division possibly through chromosomal aberrations. P. harmala alkaloids induced different types of chromosome aberrations including rings, breaks, polyploidy, sticky, laggards and bridges with the sticky form as the most abundant type. Furthermore, P. harmala alkaloids induced a significant increase in sister chromatid exchange (SCE) compared to untreated controls. The frequency of micronuclei was increased with increasing the concentration but was not affected by increasing the exposure time. The medicinal use of harmala should be under control since higher doses and/ or longer exposure is genotoxic. An amount of plant that contains ≥ 12 mg alkaloids cannot be safe for traditional use. Key words: Peganum harmala, genotoxicity, chromosome aberration, sister chromatid exchange.

Genotoxic Effects of the Anti-Cancer Drug Doxorubicin (Dxr) in the Bone Marrow Cells of Swiss Albino Mice (Mus musculus)

The antineoplastic chemotherapeutic agent doxorubicin (DXR) is probably the most utilized drug for treating many human cancers. In the current study we aimed to evaluate the genotoxic effects of doxorubicin Swiss mice bone marrow cells using the toxicological endpoints chromosomal aberrations, mitotic index and micronuclei formation. Twelve male animals, aged 6-8 weeks and weighing 24±2g were divided into four groups. One group served as control was intraperitoneally injected only with distilled water. The three remaining groups were injected intraperitoneally with single doses of doxorubicin (0.2, 0.4 and 0.8 mg/g body weight) for two consecutive days. 24 hours later, animals were anaesthetized and killed by cervical dislocation. Colchicine (0.05 %) was injected to animals 90 minutes before sacrifice. After sacrificing the animals, both femurs were dissected out and the bone marrow cells obtained. All treatments with doxorubicin caused an increased significance in the incidence of chromosomal aberrations (CA) and micronuclei formation in polychromatic erythrocytes (PCEs) cells. Meanwhile, there was a gradual repression in the mitotic index (MI) percentages of the treated groups compared to that of the control. Different types of chromosomal aberrations (structural and numerical) were induced as a result of doxorubicin treatments. These includes: gaps, breaks, fragments, rings, centric fusions (CF) and polyploidy. The mean percentages of total chromosomal aberrations increased from 3.33 ± 0.28 in the control group to 12.67 ± 2.42, 29.00 ± 4.27 and 38.67 ± 2.82 for doses 0.2, 0.4 and 0.8 mg/kg B.W. respectively. The numbers of micronucleated PCEs observed in mice cells treated with doxorubicin were increased from 4.67±0.48 for the control group to 7.00±1.02, 10.67±2.10 and 17.67 for the three doses respectively. Meanwhile, the PCE / (PCE+NCE) ratio calculated in treated animals were 0.85 ± 0.02, 0.63 ± 0.08 and 0.54 ± 0.10 compared to 0.94 ± 0.12 for the control. Our results indicated that doxorubicin has genotoxic as well as cytotoxic effects in mice bone marrow cells.

Cytological and phytochemical studies on Mesembryanthemum nodiflorum L.

Mesembryanthemum nodiflorum L. (Aizoaceae) has long been used as food and in traditional medicine. This study was intended to explore the active groups within M. nodiflorum ethanolic extract and to study the cytological effects of M.nodiflorum water extract on Allium cepa L. root tips. Phytochemical analysis of M.nodiflorum ethanolic extract indicated the presence of alkaloids and triterpenes. Tannins, flavonoids and saponins did not found in M.nodiflorum alcoholic extract. Mitotic indices and distribution of cells in mitotic phases of A.cepa root tips were clearly changed after treatment with three different concentration of M.nodiflorum water extract (0.1, 1 and 3%) for 3h, 6h, and 12h. The maximum value of mitotic index 2.68% was observed after treatment with 3% for 6h, while the minimum value 1.35% was scored after 12h exposure to the same concentration. Different types of chromosomal aberrations were noticed. The present study revealed that M.nodiflorum water extract has a potent inhibitory effect on the mitotic activity of A.cepa root tip cells.

Effects of Valproic Acid on Radiation-Induced Chromosomal Aberrations in Human Lymphocytes.

One of the most widely employed histone deacetylases inhibitors in the clinic is the valproic acid (VA), proving to have a good tolerance and low side effects on human health. VA induces changes in chromatin structure making DNA more susceptible to damage induction and influence DNA repair efficiency. VA is also proposed as a radiosensitizing agent. To know if VA is suitable to sensitize human lymphocytes γ-irradiation in vitro, different types of chromosomal aberrations in the lymphocytes, either in the absence or presence of VA, were analyzed. For this purpose, blood samples from four healthy donors were exposed to γ-rays at a dose of 1.5 Gy and then treated with two different doses of VA (0.35 or 0.70 mM). Unstable and stable chromosomal aberrations were analyzed by means of fluorescence in situ hybridization. Human lymphocytes treated with VA alone did not show any increase in the frequency of chromosomal aberrations. However, a moderate degree of sensitization was observed, through the increase of chromosomal aberrations, when 0.35 mM VA was employed after γ-irradiation, whereas 0.70 mM VA did not modify chromosomal aberration frequencies. The lower number of chromosomal aberrations obtained when VA was employed at higher dose after γ-irradiation, could be related to the induction of a cell cycle arrest, a fact that should be taken into consideration when VA is employed in combination with physical or chemical agents.

Analysis of α-particle-induced chromosomal aberrations by chemically-induced PCC. Elaboration of dose-effect curves

In a similar way to high-dose exposures to low-LET radiations, cells show difficulties reaching mitosis after high-LET radiation exposure. For this reason, techniques have been proposed that are able to analyze chromosome aberrations in interphase by prematurely condensing the chromosomes (PCC-techniques). Few dose-effect curves for high-LET radiation types have been reported, and none for α-particles. The aim of this study was to evaluate, by chemically-induced PCC, the chromosome aberrations induced by several doses of α-particles. Monolayers of peripheral lymphocytes were exposed to an α-source of Americium-241 with a mean energy entering the cells of 2.7 MeV. Lymphocytes were exposed to 10 doses, from 0–2.5 Gy, and then cultured for 48 h. Colcemid and Calyculin-A were added at 24 and 1 h before harvesting, respectively. During microscope analysis, chromosome rings and extra chromosome pieces were scored in G2/M-PCC and M cells, while dicentric chromosomes were only scored in M cells. As the dose increased, fewer cells were able to reach mitosis and the proportion of G2/M-PCC cells increased. Chromosome rings were hardly observed in M cells when compared to G2/M-PCC cells. Extra fragments were more frequent than rings in both G2/M-PCC and M cells, but with lower frequencies than in G2/M-PCC cells. The distribution of dicentrics and extra fragments showed a clear overdispersion; this was not so evident for rings. The dose-effect curves obtained fitted very well to a linear model. Damaged cells after α-particle irradiation show more difficulties in reaching mitosis than cells exposed to γ-rays. After α-particle irradiation the frequency of all the chromosome aberrations considered increased linearly with the dose, and α-particles clearly produced more dicentrics and extra chromosome pieces with respect to γ-rays. After α-particle exposure, the existence of extra chromosome fragments in PCC cells seems to be a good candidate for use as a biomarker for dose assessment. However, the observed frequencies of different types of chromosomal aberrations could be influenced by some methodological aspects; for this reason, and in order to avoid possible methodological bias, standardization of the technique will be desirable.

Dynamics of chromosomal aberrations, induction of apoptosis, BRCA2 degradation and sensitization to radiation by hyperthermia.

Hyperthermia can transiently degrade BRCA2 and thereby inhibit the homologous recombination pathway. Induced DNA-double strand breaks(DSB) then have to be repaired via the error prone non-homologous end-joining pathway. In the present study, to investigate the role of hyperthermia in genotoxicity and radiosensitization, the induction of chromosomal aberrations was examined by premature chromosome condensation and fluorescence insitu hybridisation(PCC-FISH), and cell survival was determined by clonogenic assay shortly(0-1h) and 24h following exposure to hyperthermia in combination with ionizing radiation. Prior to exposure to 4Gy γ-irradiation, confluent cultures of SW‑1573(human lung carcinoma) and RKO(human colorectal carcinoma) cells were exposed to mild hyperthermia(1h, 41˚C). At 1h, the frequency of chromosomal translocations was higher following combined exposure than following exposure to irradiation alone. At 24h, the number of translocations following combined exposure was lower than following exposure to irradiation only, and was also lower than at 1h following combined exposure. These dynamics in translocation frequency can be explained by the hyperthermia-induced transient reduction of BRCA2 observed in both cell lines. In both cell lines exposed to radiation only, potentially lethal damage repair(PLDR) correlated with a decreased number of chromosomal fragments at 24h compared to 1h. With combined exposure, PLDR did not correlate with a decrease in fragments, as in the RKO cells at 24h following combined exposure, the frequency of fragments remained at the level found after 1h of exposure and was also significantly higher than that found following exposure to radiation alone. This was not observed in the SW‑1573 cells. Cell survival experiments demonstrated that exposure to hyperthermia radiosensitized the RKO cells, but not the SW‑1573 cells. This radiosensitization was at least partly due to the induction of apoptosis, which was only observed in the RKO cells and which may have been induced by BRCA2 degradation or different types of chromosomal aberrations. An important observation of this study is that the genotoxic effect of hyperthermia shortly after combined epxosure (to hyperthermia and radiation) is not observed at 24h after treatment.

In vitroandin vivogenotoxicity and molecular response of silver nanoparticles on different biological model systems

AbstractIn vitro and in vivo experiments on human cell lines (breast adenocarcinoma, MCF-7, and liver hepatocellular carcinoma, HepG2), plants (Allium cepa) and bacteria (Staphylococcus aureus and Pseudomonas aeruginosa) displayed cytotoxic and genotoxic impacts of silver nanoparticles (AgNPs). The cell viability assays indicated that AgNPs had inhibitory effects on MCF-7 cell line more effectively than HepG2 cell line. Mitotic indices and distribution of cells in mitotic phases of A. cepa were clearly changed after treatment with three different weight ratios of silver metal (1, 3 and 5%) for 3 and 12 h. With increasing concentration of the nanoparticles a decrease in the mitotic index was detected (from 4.19 to 0.79 after 3 h and from 4.56 to 0.25 after 12 h) and different types of chromosomal aberrations were noticed. Protein electrophoresis results of S. aureus and P. aeruginosa demonstrated the change in the protein profiles of the two bacterial strains and it was more noticeable in P. aeruginosa tha...

Computer assisted human karyotyping – an analysis of 131 cases

Introduction: Karyotyping is the process of pairing and ordering all the chromosomes of an organism, thus providing a genome-wide snapshot of an individual’s chromosome. G-banded karyograms are routinely used to diagnose a wide range of chromosomal abnormalities in individuals. Although the resolution of chromosomal changes detectable by G-banded karyotyping is typically a few megabases, this can be sufficient to diagnose certain categories of abnormalities. Objectives: The primary aim of this study was to investigate the different types of chromosomal aberrations and their relative frequencies in a group of referred patients with suspected genetic disorders. Methods: This observational study was carried out at Armed Forces Institute of Pathology (AFIP) for a period of two years from January 2011 to December 2012. A total of 131 patients were included in this study. These patients were referred to AFIP from different Combined Military Hospitals (CMH) of Bangladesh Army and also from civil medical installations. All the patients were subjected to full genetic study; complete genetic examination and pedigree construction was done to exclude nonchromosomal causes of anomaly. Detailed history and physical findings were also noted in a prescribed format. The study included peripheral lymphocyte culture by a standard method using the G–banding technique. 32 JAFMC Bangladesh. Vol 9, No 2 (December) 2013 Results: Out of 131 patients, 54 (42.2%) were male and 77 (57.8%) were female with male to female ratio 0.7:1. The age limit of the patient ranges from 04 days to 70 years. Most of the patients (32.1%) were in the age group of 0–10 years followed by 21–30 year age group (30.5%). Consanguineous marriage was found in 15 (11.5%) cases in which 3 (2.3%) cases had chromosomal aberrations. Recurrent abortion was the main clinical indication (18.3%) followed by infertility (15.3%). Chromosomal aberrations were detected in 26 patients (19.8%); of these, 20 (15.2%) involved autosomes, while only 6 (4.6%) involved gonosomes. Trisomy 21 was detected in 12 (9.1%) patients and Philadelphia chromosome was found in 8 (6.1%) patients. Turner syndrome was detected in 5 (3.8%) patients and Klinefelter syndrome was found in 1 (0.8%) patient. Conclusion: The precise delineation of different types of chromosomal aberrations is only possible using clinical examination and advanced cytogenetic tools by experienced cytogeneticists. DOI: http://dx.doi.org/10.3329/jafmc.v9i2.21823 Journal of Armed Forces Medical College Bangladesh Vol.9(2) 2013

Chromosomal Abnormalities among Petrol Station Workers Occupationally Exposed to Benzene

It is known that the vast majority of malignancies are the result of genetic and environmental interactions. Fuel (diesel and petrol) constitutes a complex mixture of benzene, toluene and xylene and other monocyclic, aromatic, aliphatic and polycyclic aromatic hydrocarbons; benzene being the most hazardous because of its carcinogenic potency. This study aims to evaluate the genotoxic effects of occupational exposure to benzene through cytogenetic analysis at low levels of exposure also to investigate the possibility of liver and kidney affections. The studied group comprised 40 workers from 3 different petrol stations occupationally exposed to benzene and 20 control subjects. The two studied groups were matched regarding age and sex. Results show significant difference between exposed workers and control group in chromosomal abnormalities regarding mitotic index, gap, isogap and break. Regarding period of exposure, the frequency of different types of chromosomal aberrations was relatively high during first few years of exposure and decrease with Original Research Article El Mahdy et al.; BJAST, 7(5): 502-513, 2015; Article no.BJAST.2015.168 503 increasing duration. Regarding liver function tests, levels were within normal ranges but higher in workers with statistically significant difference between exposed workers and control group and they were significantly correlated with the duration of exposure (p value= .05). Occupational exposure to mutagenic and carcinogenic agents creates a significant impact on the health status of gasoline station attendants. Identification and prevention of possible health problems related to such exposure would help in maintaining good health of workers; prevent reduction in working capacity and loss of working hours besides reducing the cost of medical care for affected workers. Further studies are needed to assess DNA status in the lymphocytes that might be a predictor of future cancer risks and might help to prevent further deterioration in the health of these workers.

Toxopathological and cytogenetic effects of aflatoxin B1 (AFB1) on pregnant rats

The present study was carried out to evaluate the toxopathological effects and macro-DNA damage of Aflatoxin B1 (AFB1) in pregnant rats at a dose of 1mg/kg. body wt., given from 6th to 15th day of gestation. The effects and damage are represented by histopathological changes and different types of chromosomal aberrations in dams, in addition to teratogenic changes in the feti. Pregnant dams revealed a significant decrease in their body weights and gross enlargement of the liver. Histologically, the liver showed necrotic areas and congested central vein. The kidneys revealed interstitial hemorrhages, renal casts, degeneration and necrosis. The lungs revealed lymphocytic infiltrates in the interstitial tissue, while the spleen revealed lymphoid depletion. Chromosomal analysis revealed both structural and numerical chromosomal aberration, including centromeric attenuations, chromatid gaps, chromatid breaks, end-to-end associations, fragments, ring chromosomes, deletions, dicentric chromosomes, chromosomal fusions, centric fusions, stickness and hypoployploidy. Centromeric attenuations and end-to-end associations were more frequent than other chromosomal aberrations. Concerning the teratogenic effects in the fetuses, the toxin induced multiple skeletal anomalies. These anomalies included incomplete ossification of skull bones and failure of ossification of long and flat bones.

Generalized Time-Dependent Model of Radiation-Induced Chromosomal Aberrations in Normal and Repair-Deficient Human Cells

We have developed a model that can simulate the yield of radiation-induced chromosomal aberrations (CAs) and unrejoined chromosome breaks in normal and repair-deficient cells. The model predicts the kinetics of chromosomal aberration formation after exposure in the G₀/G₁ phase of the cell cycle to either low- or high-LET radiation. A previously formulated model based on a stochastic Monte Carlo approach was updated to consider the time dependence of DNA double-strand break (DSB) repair (proper or improper), and different cell types were assigned different kinetics of DSB repair. The distribution of the DSB free ends was derived from a mechanistic model that takes into account the structure of chromatin and DSB clustering from high-LET radiation. The kinetics of chromosomal aberration formation were derived from experimental data on DSB repair kinetics in normal and repair-deficient cell lines. We assessed different types of chromosomal aberrations with the focus on simple and complex exchanges, and predicted the DSB rejoining kinetics and misrepair probabilities for different cell types. The results identify major cell-dependent factors, such as a greater yield of chromosome misrepair in ataxia telangiectasia (AT) cells and slower rejoining in Nijmegen (NBS) cells relative to the wild-type. The model's predictions suggest that two mechanisms could exist for the inefficiency of DSB repair in AT and NBS cells, one that depends on the overall speed of joining (either proper or improper) of DNA broken ends, and another that depends on geometric factors, such as the Euclidian distance between DNA broken ends, which influences the relative frequency of misrepair.

Ameliorative Potential of Mesenchymal Stem Cells and Hematopoietic Stem Cells against CCl&amp;lt;sub&amp;gt;4&amp;lt;/sub&amp;gt; Induced Chromosomal Abnormalities in Experimental Rat Liver Fibrosis

Background and Objective: The liver is responsible for metabolism and detoxification of the most of components that enter the body. Once the liver became injured, its efficient treatment with famous chemical drugs was limited. Therefore, interest concerned the use of alternative medicines for the treatment of hepatic disease has been arisen. The present study was aimed to investigate the therapeutic effect of the two types of stem cells against chromosomal aberrations in bone marrow (BM) cells of rats treated with carbon tetrachloride (CCl4). Design and Method: BM-derived mesenchymal stem cells (MSCs) were isolated and propagated in culture for 2 weeks and were characterized morphologically. Human umbilical cord blood (UCB) cells were obtained after full-term caesarean delivery from healthy donors. Low-density mononuclear cells were separated over Ficoll-Paque, and CD34+ hematopoietic cells were isolated using a magnetic cell sorter. Rats were divided into 4 groups: control, CCl4, CCl4 plus MSC, and CCl4 plus CD34+. Liver tissue was examined histopathologically for all groups. Results: The results of the present study indicated a significant increase (p ＜ 0.05) in the number of metaphases with different types of chromosomal aberrations in CCl4 group. Treatment of the animals with BM-MSCs and UCB-CD34+ cells improved both genotoxicity and histopathological changes induced by CCl4.

Radioprotective effects of Dragon's blood and its extract against gamma irradiation in mouse bone marrow cells

PurposeThe radioprotective effects of Dragon's blood (DB) and its extracts (DBE) were investigated using the chromosomal aberrant test, micronucleus and oxidative stress assay for anti-clastogenic and anti-oxidative activity. Materials and methodsAdult BALB/C mice were exposed to the whole body irradiation with 4 Gy 60Co γ-rays. DB and DBE were administered orally once a day from 5 days prior to irradiation treatment to 1 day after irradiation. The mice were sacrificed on 24 h after irradiation. The cells of bone marrow were measured by counting different types of chromosomal aberrations and the frequency of micronuclei. Oxidative stress response was carried out by analysis of serum from blood. ResultsDB and DBE significantly decreased the number of bone marrow cells with chromosome aberrations after irradiation with respect to irradiated alone group. The administration of DB and DBE also significantly reduced the frequencies of micronucleated polychromatic erythrocytes (MPCE) and micronucleated normochromatic erythrocytes (MNCE). In addition, DB and DBE markedly increased the activity of antioxidant enzymes and the level of antioxidant molecular. Malondialdehyde (MDA) and nitric oxide (NO) levels in serum were significantly reduced by DB and DBE treatment. ConclusionsOur data suggested that DB and DBE have potential radioprotective properties in mouse bone marrow after 60Co γ-ray exposure, which support their candidature as a potential radioprotective agent.