scholarly journals Assessment of genotoxic potential of the insecticide Dichlorvos using cytogenetic assay

2013 ◽  
Vol 6 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Nazia Nazam ◽  
Mohammad Iqbal Lone ◽  
Sibhghatulla Shaikh ◽  
Waseem Ahmad

Abstract The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD50 for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; X2 test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non-genotoxic mechanisms.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4899-4899
Author(s):  
Zonghong Shao ◽  
Huaquan Wang ◽  
Jun Shi ◽  
Yanran Cao ◽  
Hong Liu ◽  
...  

Abstract Background Myelodysplastic syndromes (MDS) is a group of clone haematopoietic stem cell diseases. The burden of abnormal hematopoietic clone plays key roles in the development of this disease and needs to be further studied quantitively. Methods The ratio of the counted bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, the ratio of cFU-GM to CFU-GM, micromegakaryocyte, transfusion, IL-2, TNF, CD4+ and CD8+ T cells of MDS patients were assayed and the correlations between those parameters and MDS clone burden were also analysed. Results The clone burden of MDS patients was (67.4±36.2)%. MDS clone burden correlated positively with bone marrow blasts(r =0.483, P=0.012), negatively with hemoglobin level(r = −0.445, P= 0.023); The number of blasts, hemoglobin and erythocytes in high clone burden(&gt;50%) and low clone burden(≤50%) groups were (7.78±5.51)% and (3.45±3.34)%(P=0.035), (56.06±14.28)g/L and (76.40±24.44)g/L(P=0.013), (1.82±0.12)×1012/L and (2.32±0.21)×1012/L(P=0.034)respectively. CD4+ T lymphcytes of MDS patients and normal controls were (274.18±71.85)×106/L and (454.82±205.88)×106/L(P=0.012)respectively. CD8+ T lymphcytes of MDS patients and normal controls were (240.45±150.01)×106/L an (305.27±145.14)×106/L(P=0.317)respectively. The serum level of interleukin 2 of MDS patients and normal control group were (6.29±3.58)ng/ml and (3.11±1.40)ng/ml (P=0.002) respectively. The serum level of tumor necrosis factor of MDS patients and normal control group were (2.42±1.79)ng/ml and (1.68±0.69)ng/ml(P=0.124)respectively. The ratio of CD4 to CD8 in high clone burden MDS patients was (1.90±0.52), and that in low clone burden patients was (0.97±0.44)(P=0.022). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severeity and prediciting it’s progression.


2009 ◽  
Vol 25 (7) ◽  
pp. 467-471 ◽  
Author(s):  
BN Mojidra ◽  
K. Archana ◽  
AK Gautam ◽  
Y. Verma ◽  
BC Lakkad ◽  
...  

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.


2020 ◽  
Vol 28 (4) ◽  
pp. 480-486 ◽  
Author(s):  
Pankaj Tripathi ◽  
Saeed Alshahrani ◽  
Hassan A. Alhazmi ◽  
Rina Tripathi ◽  
Abdul Hakeem Siddiqui ◽  
...  

2005 ◽  
Vol 59 (5-6) ◽  
pp. 549-556
Author(s):  
Milan Kulic ◽  
Zoran Stanimirovic ◽  
Sinisa Ristic ◽  
Biljana Markovic

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.


2006 ◽  
Vol 60 (1-2) ◽  
pp. 3-9
Author(s):  
Milan Kulic ◽  
Zoran Stanimirovic ◽  
Biljana Markovic ◽  
Sinisa Ristic

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.


Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4136-4142 ◽  
Author(s):  
I Kawashima ◽  
ED Zanjani ◽  
G Almaida-Porada ◽  
AW Flake ◽  
H Zeng ◽  
...  

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.


1984 ◽  
Vol 26 (2) ◽  
pp. 152-157
Author(s):  
S. M. Singh ◽  
D. L. Reimer

Frequency of sister chromatid exchanges (SCE) were recorded separately for different chromosomes from bone marrow cells of female mice of the two genetic strains (C3H/S and C57BL/6J). SCEs were evaluated following different doses of 5-bromo-2′deoxyuridine (BrdU) as nine hourly i.p. injections. The SCE per cell increased with increasing BrdU doses which was slightly higher in C3H/S than in the C57BL/6J. SCEs per cell were variable at every treatment – strain combination, possibly reflecting the heterogeneous nature of the bone marrow cells. In general, there is a positive correlation between SCE per chromosome and the relative chromosome length. Total SCEs on one of the large chromosomes (most likely the X chromosome), however, are significantly higher than expected on the basis of relative length alone. Most of this increase is attributable to one of the homologues of this chromosome, which is not in synchrony with the rest of the chromosomes and may represent the late-replicating X. These results when viewed in the light of replication properties of the heterochromatinized X, suggest a direct involvement of DNA replication in SCE formation and may argue against the replication point as the sole site for the SCEs.Key words: sister chromatid exchange, BrdU, recombination, replication, X chromosome.


Blood ◽  
2013 ◽  
Vol 121 (12) ◽  
pp. e90-e97 ◽  
Author(s):  
Mark Wunderlich ◽  
Benjamin Mizukawa ◽  
Fu-Sheng Chou ◽  
Christina Sexton ◽  
Mahesh Shrestha ◽  
...  

Key Points A relevant xenograft chemotherapy model was developed by using standard AML induction therapy drugs and primary human AML patient samples. Human AML cells show significantly increased sensitivity to in vivo chemotherapy treatment compared with murine LSK and total bone marrow cells.


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