Chromosomes Of Bone Marrow Cells Research Articles

Efficacy and functionality of sugarcane original vinegar on mice.

Due to their bioactive compounds and beneficial health effects, functional foods and plant-based natural medicines are widely consumed. Due to its bioactivities, vinegar is one of them that helps humans. Sugarcane original vinegar (SOV) is a special vinegar made from sugarcane as a raw material through biological fermentation processes. The objective of this study was to assess the effects of sugarcane original vinegar on growth performance, immune response, acute oral toxicity, bacterial reverse mutation, mammalian erythrocyte micronucleus, mouse spermatogonial chromosome aberration, mammalian bone marrow cell chromosome aberration changes, and serum characteristics in mice. Distortion parameters were used to assess its safety, and at the same time, the functionality of SOV was monitored during experimentation. The results show that the SOV has no damage or inhibitory effect on the bone marrow red blood cells of mice and no mutagenic or distortion-inducing effects on the bone marrow cell chromosomes or spermatogonia chromosomes, so it is safe to eat. SOV can improve blood lipids and reduce blood lipid content. The study results provide data basis for the intensive processing of sugarcane and the development of high-value SOV products. Sugarcane original vinegar has a beneficial impact on performance, immune response, and chromosomal aberration. The production application influences the vinegar's quality and, consequently, its health benefits.

Cytogenetic Effects Of Fumagillin On Male Mice (Mus musculus)

The cytogenetic effects of Fumagillin were evaluated according to Mitotic Index (M.I) and aberration of metaphase chromosomes in bone marrow cells(CA) of white mice. The fumagillin was given as repeated oral gavages for 7 successive days after preparing the doses 10,15 at concentrations 20 mg/kg.b.wt. in 50% of sugar syrup . The positive control was given single I.p. dose of 20 mg/kg.b.wt. of methotrexate. The three dosages 10, 15, and 20 mg/kg.b.wt of Fumagillin induced significant decrease in mitotic index (3.90 ± 0.29, 3.60 ± 1.80, and 2.90 ±0.18) respectively compared with (7.10 ±0.29) for negative control. The results showed that the two dosages 15 and 20 mg/kg.b.wt of Fumagillin induced significant increase in the frequency of the chromosome aberration in bone marrow cells of the mice in the these groups (9.00± 0.92, 17.20 ± 1.42) respectively compared with (6.00 ±0.83) for negative control. The obtained result revealed the genetic and cellular toxic reaction of Fumagillin within the high and medium limits studied doses.

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents.

The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.

Effect of Carbafuran Pesticide on Mitotic Chromosomes of Mus musculus

The Genotoxic effect of the carbafuran pesticide was evaluated in the metaphasic chromosomes of bone marrow cells of female Swiss albino mice, Mus musculus . Six week old mice were put into different groups(six mice per group) and treatment were done according to experimental plan (CLD15 i.e. lower dose =30ppm or 0.03mg/ml and CHD30 i.e. higher dose =300ppm or 0.3mg/ml).The test material was administered orally for 15 days in CLD15 and for 30 days in CHD30 test groups of female mice. The result revealed that the frequency of chromosomal abnormalities i.e. structural and numerical changes were11.5% in control, 74.0%in CLD15 and 99.0%in CHD30, respectively in bone marrow cells of female mice.Int. J. Appl. Sci. Biotechnol. Vol 6(2): 169-173

Chromosomal abnormalities in bone marrow cells in relapse of chronic lymphocytic leukemia

The genetic mechanism of resistance to chemotherapy in chronic lymphocytic leukemia (CLL) is yet to be established. We aimed to determine molecular cytogenetic irregularities in chromosomes of bone marrow cells (BM) in relapse of CLL. For this, a study was carried out with 63 patients including 25 women and 38 men, aged from 36 to 73 years (average age was 57 years). Cytogenetic data showed that karyotypes, according to the clone structure, were represented into 10 groups: normal; normal/near tetraploid; abnormal/normal; abnormal/near tetraploid/normal; clonal evolution; clonal evolution/normal; clonal evolution/near tetraploid/normal; independent clones; independent/normal; independent/near tetraploid/normal clones. Various structural rearrangements were detected in chromosomes such as translocations, deletions, insertions and duplications. However, deletions in chromosomes were found to be dominant in 63.8% cases involving the band positions of especially 17p12, 13q12–q14, 11q14 and 11q23. The complexity was shown by the presence of one to four abnormalities in one karyotype using i-FISH methodology. Conventional cytogenetic and molecular cytogenetic analyses may indicate that chromosome rearrangements are multilevel process in formation of resistant karyotypes either through the loss of (1) tumour suppressor genes in the areas with bands 13q14, 13q34 and 17p13.1 (2) and/or the loss of regulation of ATM gene expression in the band position 11q22.3. The results obtained using both methods have demonstrated the presence of a heterogeneous cell population with a diverse degree of resistance to chemotherapy in CLL.

Expression and Clinical Significance of Focal Adhesion Kinase in Patients with Acute Leukemia

To explore the expression of focal adhesion kinase (FAK) in patients with acute leukemia (AL) and its clinical significance. The FAK mRNA levels in leukemic cells of 50 patients with AL and bone marrow mononuclear cells(BMMNC) of 10 healthy controls were measured by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The bone marrow cell chromosomes were prepared using direct and short term culture, and karyotyping was performed by R-banding technique. The expression positive rate of FAK mRNA in leukemic cells of 50 patients with AL was 66.0%, which was significantly higher than that in normal controls (20.0%) (P<0.05). The expression positive rates and levels of FAK mRNA in both ALL and ANLL cells were statistically significantly higher than those in normal controls (P<0.05), but the difference between ALL and ANLL cells was not significant (P>0.05). All the expression- positive rates and levels of FAK mRNA in newly diagnosed AL patients and the relapsed AL patients were significantly higher than those in normal controls (P<0.05), but the difference between the newly diagnosed AL patients and the relapsed AL patients was not significant (P>0.05). Morecover, the expression plsitive rate and levels of FAK mRNA in the remitted patients were lower than those in newly diagnosed and relapsed patients (P<0.05), but were no statistically significantly different from normal controls (P>0.05). The expression- positive rate and level of FAK mRNA in the AL patients with abnormal karyotype were significantly higher than those in the AL patients without abnormal karyotype (P<0.05). FAK mRNA over-express in the leukemia patients, which may be related with the outome of disease, possibly providing novel targeting sites for the treatment of leukemia.

Sequencing the AML Genome, Transcriptome, and Epigenome

Leukemia is a disease that develops as a result of changes in the genomes of hematopoietic cells, a fact first appreciated by microscopic examination of the bone marrow cell chromosomes of affected patients. These studies revealed that specific subtypes of leukemia diagnoses correlated with specific chromosomal abnormalities, such as the t(15;17) of acute promyelocytic leukemia and the t(9;22) of chronic myeloid leukemia. Over time, our genomic characterization of hematologic malignancies has moved beyond the resolution of the microscope to that of individual nucleotides in the analysis of whole-genome sequencing (WGS) data using state-of-the-art massively parallel sequencing (MPS) instruments and algorithmic analyses of the resulting data. In addition to studying the genomic sequence alterations that occur in patients' genomes, these same instruments can decode the methylation landscape of the leukemia genome and the resulting RNA expression landscape of the leukemia transcriptome. Broad correlative analyses can then integrate these 3 data types to better inform researchers and clinicians about the biology of individual acute myeloid leukemia (AML) cases, facilitating improvements in care and prognosis.

Effect of resveratrol on chromosomal aberrations induced by doxorubicin in rat bone marrow cells

This study investigated the effects of resveratrol (RES) on doxorubicin (DXR) induced rat bone marrow cell chromosome aberrations. RES, a polyphenolic compound, has attracted considerable attention because of its antioxidant and antimutagenic effects. DXR, a chemotherapeutic agent, is known to cause chromosomal aberrations in healthy cells in cancer patients. In this study, Wistar albino male rats were divided into 6 groups with 6 animals each. The control group received distilled water i.p. and the DXR group received an i.p. injection of doxorubicin (90mg/kgbw). For the 2 RES dose groups (12.5 and 25mg/kgbw, respectively), RES was injected i.p. 5 times during the 24h study period to coincide with the schedule for the DXR+RES groups. The DXR-RES groups received DXR (90mg/kgbw) and RES at either 12.5 or 25mg/kgbw, i.p. 30min before, concurrently, and then every 6h after DXR administration. Bone marrow collection was timed to coincide with 24h after DXR administration in all groups. RES administration alone did not induce any significant increase in frequency of chromosome aberrations or abnormal metaphases compared with controls (p>0.05) while DXR alone did (p<0.05). In the DXR-RES 12.5mg/kgbw group, frequency of chromosome aberrations and abnormal metaphases were slightly reduced compared to DXR alone, but this was not statistically significant. However, in the DXR-RES 25mg/kgbw group, RES resulted in a statistically significant reduction in the frequency of chromosome aberrations and abnormal metaphases compared to those induced by DXR alone (p<0.05). These results indicate that RES (25mg/kgbw) significantly reduces frequency of DXR induced chromosome damage in bone marrow cells.

Detection of Philadelphia Chromosome in Patients with Chronic Myeloid Leukemia from the Prešov Region in Slovakia (1995-2004)

Philadelphia chromosome (Ph) is a characteristic chromosomal marker that is associated with chronic myelogenous leukemia (CML). Philadelphia chromosome in bone marrow cells in patients with suspected diagnosis of CML in the Presov region (1995-2004) was detected in 94.4 % of cases. In one patient a complex translocation involving the chromosomes 8, 9 and 22 was identified. One patient has showed extra numerical and structural chromosomal aberrations. The mosaic karyotype of Ph chromosome was found in 5.9 % of cases. The conventional cytogenetic analysis remains the standard method for the purpose of diagnosis and monitoring of the therapeutic response and minimal residual disease in patients with chronic myeloid leukemia (Tab. 1, Fig. 1, Ref. 18). Full Text (Free, PDF) www.bmj.sk.

Investigations of genotoxic potential of levamisole hydrochloride in bone marrow cells of Wistar rats

An experiment was performed under in vivo conditions on bone marrow cells of Wistar rats. The following doses of levamisole hydrochloride were tested: a therapeutic dose of 2.2 mg/kg bm, a dose of 4.4 mg/kg bm, LD50 -25% mg/kg bm, and LD50 -75% mg/kg bm. We followed the effect of levamisole hydrochloride on kinetics of the cell cycle and the appearance of structural and numeric changes in chromosomes in bone marrow cells. The therapeutic dose of levamisole of 2.2 mg/kg bm exhibited a capability to increase mitotic activity in the observed cells, thus confirming knowledge of the immunostimulative effect of this dose of the medicine under in vivo conditions. The other tested doses of levamisole in this experiment, observed in comparison with the control group, had an opposite effect, namely, they caused a reduction in the mitotic activity of bone marrow cells. All the examined doses in vivo exhibited the ability to induce numeric (aneuploid and polyploid) and structural (lesions, breaks and insertions) chromosomal aberrations. It can be concluded on the grounds of these findings that the examined doses have a genotoxic effect.

The cytogenetic effect of the new asthma and allergy drug montelukast on albino mice: chromosomal studies

Montelukast or Singulair has recently been introduced to treat asthma. Because it is apparently free of serious side-effects, the present work aimed to investigate its effects on chromosomes of bone marrow cells of mice. The percentage of structural chromosomal aberrations was highly elevated due to treatment with Montelukast. The aberrations increased successively with increasing the time and the dose of the therapy. Numerical chromosomal aberrations were also increased, and interstitial deletions of certain bands were detected in G/T-banded karyotypes of the treated samples. Montelukast appears to have potential genotoxicity in the somatic cells of mice in vivo.

In vivo investigations of clastogenic effect of levamisole hydrochloride on bone marrow cells of BALB/c mice

Cytotoxic and genotoxic examinations were performed of the effect of levamisole hydrochloride (2.2 mg/kg bm, 4.4 mg/kg bm, LD50-25% mg/kg bm and LD50-75% mg/kg bm) on bone marrow cells of mice of the BALB/c strain. The effect of levamisole hydrochloride on kinetics of the cellular cycle and the appearance of structural and numerical changes in chromosomes of bone marrow cells were followed. The therapeutic dose of levamisole of 2.2 mg/kg bm showed the ability to increase the mitotic activity of the observed cells, thus confirming knowledge of the immunostimulative effect of this dose of the medicine under in vivo conditions. The other tested doses of levamisole in this experiment, observed in comparison with the control group, had an opposite effect, i.e. they caused a reduction in the mitotic activity of bone marrow cells. All the examined doses in vivo showed the ability of inducing numeric (aneuloid and polyploid) and structural (lesions, breaks and insertions) chromosomal aberrations. On this basis, it can be concluded that the examined doses have a genotoxic effect.

Changes in antigenic characteristics of erythrocytes and number metaphase chromosome in bone marrow cells after experimental and clinical bone marrow transplantation.

Transplantation of allogenic bone marrow from HLA-identical sibs to patients with acute and chronic leukemia receiving immunosuppressive therapy is associated with the appearance of erythrocytes simultaneously carrying donor and recipient antigenic markers: AB0 system, rhesus factor and its subtypes, M and N antigens. Integration of genes responsible for each antigen is realized independently presumably at the level of stem cell, which ensures long-term (>3 years) repopulation of these erythrocytes. Experiments on inbred mice showed that transplantation of allogenic bone marrow is associated with an increase of chromosome number in 39% bone marrow cells 4 days after transplantation, which indicate the possibility of integration of whole chromosomes.

Aggressive Primary Plasma Cell Leukemia with Skin Manifestations, Trisomy 8 and Molecular Oligoclonal Features

Plasma cell leukemia (PCL) is a very rare variant of multiple myeloma (MM) occurring in about 2% of newly diagnosed patients. Plasma cell leukemia may develop during the course of MM (secondary PCL) or it can occur without any prior sign of MM (primary PCL). We report a case of aggressive primary PCL with unusual clinical, cytogenetic and molecular features. A 36-year-old male patient was first seen because of fever and bone pain. On the skin of his chest, back, abdomen, and palpebras, there were nodular infiltrations resembling urticaria. White blood cell count was 10.8 x 109/l with 41% plasmacytes. Bone marrow aspiration was hypercellular, 93.5% of cells were atypical plasmacytes and plasmablasts. The cytogenetic analysis of G-banded chromosomes in bone marrow cells yielded the trisomy 8. The skin biopsy specimen showed intensive infiltrates of uninucleated blastic cells similar to those found in the bone marrow. Immunophenotyping of bone marrow and skin neoplastic cells showed CD45+, CD45Ro+, CD68+, CD38+ and cytoplasmic kappa light chain +. The neoplastic cells stained negatively for lambda light chain, CD3, CD20, CD30, EMA, CD15, CD34, CD56 and factor VIII. The pattern of IgL genes rearrangement in the bone marrow aspirate, peripheral blood mononuclear cells, and skin specimens was examined by PCR analysis. All studied specimens showed three different Igκ gene configurations suggesting that the neoplastic cells originated as a result of oligoclonal lymphoproliferation process. The patient received two courses of VAD (vincristine, doxorubicin, dexamethasone) without improvement and three courses of CHOP with only temporary stabilization of the disease. He died 5 months after the diagnosis of PCL because of disease progression and pneumonia.

Toxicological, medical and industrial hygiene aspects of glutaraldehyde with particular reference to its biocidal use in cold sterilization procedures

Aqueous solutions of > or =5% glutaraldehyde (GA) are of moderate acute peroral toxicity and those of < or =2% are of slight toxicity. By single sustained skin contact, aqueous GA solutions of > or =45% are of moderate acute percutaneous toxicity, those of 25% are of slight toxicity and those of </=15% do not present an acute percutaneous hazard. Vapor generated at ambient temperature may cause sensory irritant effects to the eye and respiratory tract, but not acute respiratory tract injury. The 50% decrease in respiratory rate (rd(50)) is 13.86 ppm. A 0.1% solution of GA is not irritating to the eye; the threshold for conjunctival irritation is 0.2% and for corneal injury it is 1.0%. Eye injury is moderate at 2% and severe at > or =5%. Primary skin irritation depends on the duration and contact site, occlusion and solvent. By sustained contact, the threshold for skin irritation is 1%, above which erythema and edema are dose related. With 45% and higher, skin corrosion may occur. There is a low incidence of skin sensitizing reactions, with an eliciting threshold of 0.5% aqueous GA. However, GA is neither phototoxic nor photosensitizing. Subchronic repeated exposure studies by the peroral route show only renal physiological compensatory effects, secondary to reduced water consumption. Repeated skin contact shows only minor skin irritant effects without systemic toxicity. By subchronic vapor exposure, effects are limited to the nasal mucosa at 1.0 ppm, with a no-effect concentration generally at 0.1 ppm. There is no evidence for systemic target organ or tissue toxicity by subchronic repeated exposure by any route. A chronic drinking water study showed an apparent increase, in females only, of large granular cell lymphocytic leukemia but this was not dosage related. This is most likely the result of a modifying effect on the factor(s) responsible for the expression of this commonly occurring rat neoplasm. A chronic (2-year) inhalation toxicity/oncogenicity study showed inflammatory changes in the anterior nasal cavity but no neoplasms or systemic toxicity. In vitro genotoxicity studies--bacterial mutagenicity, forward gene mutation (HGPRT and TK loci), sister chromatid exchange, chromosome aberration, UDS and DNA repair tests--have given variable results, ranging from no effect through to weak positive. In vivo genotoxicity studies--micronucleus, chromosome aberration, dominant lethal and Drosophila tests--generally have shown no activity but one mouse intraperitoneal study showed bone marrow cell chromosome aberrations. Developmental toxicity studies show GA not to be teratogenic, and a two-generation study showed no adverse reproductive effects. Percutaneous pharmacokinetic studies showed low skin penetration, with lowest values measured in vitro in rats and human skin. Overexposure of humans produces typical sensory irritant effects on the eye, skin and respiratory tract. Some reports have described an asthmatic-like reaction by overexposure to GA vapor. In most cases this resembles reactive airways dysfunction syndrome, and the role of immune mechanisms is uncertain. Local mucosal effects may occur if medical instruments or endoscopes are not adequately decontaminated. Protection of individuals from the potential adverse effects of GA exposure requires that there be adequate protection of the skin, eyes and respiratory tract. The airborne concentration of GA vapor should be kept below the recommended safe exposure level (e.g. the threshold limit value) by the use of engineering controls. Those who work with GA should, through a training program, be aware of the properties of GA, its potential adverse effects, how to handle the material safely and how to deal with accidental situations involving GA. If effects develop in exposed workers, the reasons should be determined immediately and corrective methods initiated. (c) 2001 John Wiley & Sons, Ltd.

Simultaneous Action of Cypermethrin and Two Environmental Pollutant Metals, Cadmium and Lead, on Bone Marrow Cell Chromosomes of Rats in Subchronic Administration

The aim of the present study was to investigate the possible genotoxic effects, exerted by the pyrethroid cypermethrin and by either of the metals cadmium and lead alone or in combination, on bone marrow cell chromosomes in a subchronic experiment. Outbred male Wistar rats were treated per os for 4 weeks in a five-time per week schedule with 5.54, 11.08, or 22.16 mg/kg cypermethrin (1/100, 1/50, 1/25 LD50) alone, or in combination of 1/100 and 1/50 LD50 cypermethrin with 2.0 mg/kg cadmium chloride or 10 mg/kg lead acetate. On the day following the last treatment, the animals were sacrificed and bone marrow from the femur was prepared. Twenty metaphases from 10 animals per group were evaluated. The evaluation comprised the frequency of aberrant cells, the numerical and structural aberrations, and the alterations in relative organ weights. In the dosage used, cypermethrin and cadmium alone caused no significant increase in the chromosomal aberrations, and lead acetate caused an increase of the numerical aberrations only. Combination of cypermethrin and cadmium also failed to induce significant chromosomal effects. The cypermethrin+lead combination, however, induced a significant increase of structural chromosomal abberations, predominantly of all acentric fragments. This lead to the conclusion that the simultaneous administration of lead and cypermethrin results in an enhanced genotoxic effect.

Loss of the Y chromosome in bone marrow cells: results on 1907 consecutive cases of leukaemia and preleukaemia

Loss of the Y chromosome with a resulting 45, X0 karyotype is observed in normal bone marrow cells of elderly males but also in haematological malignancies. Whether Y loss in neoplastic cells is related to the process seen in normal ageing or is part of the carcinogenic process is unknown. The present study concerns the cytogenetic data from 1907 consecutive leukaemic or preleukaemic male patients with special regard to the presence or absence of the Y chromosome. Sixty-five patients (3.4%) had a 45, X-Y clone in their bone marrow (BM) cells. Loss of Y was rare below the age of 50 but increased in older patients, reaching 25% of the men over 80. Sixteen patients (0.08%) had more than 90% X0 cells in their BM. A correlation between Y loss and leukaemia could be established in seven cases, three of which were acute myeloid leukaemia M2 subtype where -Y is known to be a secondary event. In three other cases, -Y was part of a complex karyotype. Only one patient exhibited a 45, X0 karyotype, with no other rearrangement, that could be positively correlated with the neoplastic process.

Prolonged murine genotoxic effects of crude extracted from neem.

Oral administration of a crude ethanol extract of the leaves of neem (Azadirachta indica A juss) to adult Swiss albino mice for 7 days at 5 mg, 10 mg or 20 mg/10 g bw/day significantly increased the incidence of structural and mitosis disruptive changes in metaphase chromosomes of bone marrow cells on days 8, 15 and 35th of observation. It is proposed that one or other of the many constituents of the extract, along with genera free radicals, interfered with DNA to yield chromosome strand breakage or produced spindle disturbances, inducing belated genotoxic effects.

The effect of sheng bai solution on irradiated mice bone marrow cell division index and DNA content.

Before and after general irradiation with 60Co-gamma, mice were orally given Sheng Bai Solution (SBS) for one week. SBS alleviated the irradiation-induced reduction of bone marrow cell chromosome division index. The irradiation-induced decrease of marrow DNA amount, thymic and splenic fractions, and total leukocyte number were restored to some extent. SBS also helped to ameliorate general condition of patients.

Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats.

The ultra-long telomeres that have been observed in mice are not in accordance with the concept that critical telomere shortening is related to aging and immortalization. Here, we have used quantitative fluorescence in situ hybridization to estimate (T2AG3)n lengths of individual telomeres in various mouse strains. Telomere lengths were very heterogeneous, but specific chromosomes of bone marrow cells and skin fibroblasts from individual mice had similar telomere lengths. We estimate that the shortest telomeres are around 10 kb in length, indicating that each mouse cell has a few telomeres with (T2AG3)n lengths within the range of human telomeres. These short telomeres may be critical in limiting the replicative potential of murine cells.