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Frequencies of trisomy 1, 5 and 7 in the peripheral blood lymphocytes of workers exposed to benzene, and unexposed controls. Individual values for each study subject are presented and the median is shown as a horizontal bar. The three exposure categories are: controls ( s ), workers exposed to ഛ 31 p.p.m. ( d ) and to Ͼ 31 p.p.m. ( m ) benzene. A natural log transformation was used to normalize each outcome and a test for trend was performed by linear regression, controlling for age and gender, the original matching variables. A statistically significant increasing trend was seen for trisomy of all three chromosomes (1, P trend Ͻ 0.001; 5, P trend Ͻ 0.01; 7, P trend Ͻ 0.0001).
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Two of the most common cytogenetic changes in therapy- and chemical-related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7. The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hyb...
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Context 1
... with controls (n 44), the mean frequency of trisomy 1 in all exposed workers (n 43) was increased from 0.27 to 0.53 (P 0.01), of trisomy 5 from 0.51 to 0.88 (P 0.05) and of trisomy 7 from 0.87 to 1.66 (P 0.001). These increases in trisomy were detected especially in the 31 p.p.m. group (Figure 2). In the 31 p.p.m. group, frequencies of trisomy 1 and 5 were not significantly increased, whereas trisomy 7 showed an increase of borderline signific- ance (P 0.05). ...
Context 2
... trends were observed for chromosomes 1, 5 and 7 (P 0.05). Interestingly, all three chromosomes have very similar tetra- somy frequency levels in each category (controls, lower exposure and higher exposure) (Table II), whereas trisomy rates are quite different from one chromosome to another (Figure 2). In fact, most of the tetrasomies we detected (93%) were tetraploidy rather than real tetrasomies, which means that four copies of each chromosome were present in the same cell. ...
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... Wartości LOAEC i NOAEC dla efektów genotoksycznego działania benzenu uzyskane w badaniach osób zawodowo narażonych na benzen Table 15. LOAEC and NOAEC values for the genotoxic effects of benzene obtained in studies of occupationally exposed benzene subjects 1998a; LOAEC dla efektów genotoksycznych określono na około 6,4 mg/m 3 (2 ppm). Natomiast przy stężeniach około 2,20 mg/m 3 (0,69 ppm) takich efektów nie zanotowano (tab. ...
Benzen jest bezbarwną lub lekko żółtą cieczą o charakterystycznym zapachu. Naturalnymi źródłami benzenu są gazy emitowane z wulkanów i pożarów lasów oraz produkty ropopochodne. Benzen stosuje się przede wszystkim jako rozpuszczalnik oraz materiał wyjściowy w syntezie wielu chemikaliów. W Polsce w 2020 r. 28 osób pracowało w narażeniu na benzen o stężeniach powyżej obowiązującej wartości NDS. Benzen działa narkotycznie w warunkach zatrucia ostrego. Ciekły działa drażniąco. Po narażeniu przewlekłym u ludzi obserwowano zmiany hematologiczne we krwi oraz nowotwory, w tym ostrą białaczkę szpikową. Podobne efekty obserwowano u zwierząt laboratoryjnych. Benzen i/lub jego metabolity wykazują działanie genotoksyczne. Takie działanie benzenu wykazano u ludzi zawodowo narażonych na związek o stężeniu <3,2 mg/m3 (<1 ppm). Benzen nie jest teratogenem dla zwierząt. Jako wartość NDS dla benzenu proponuje się przyjąć stężenie rekomendowane w dyrektywie Parlamentu Europejskiego i Rady, zmieniającej dyrektywę 2004/37/WE, tj. 0,66 mg/m3. Ryzyko wystąpienia białaczki u pracowników zawodowo narażonych na benzen o stężeniu 0,66 mg/m3 mieści się w zakresie 2,7 · 10−4 ÷ 1 · 10−3. Proponuje się także dodać notacje: „Carc. 1A” (substancja rakotwórcza kategorii zagrożenia 1A); „skóra” (wchłanianie substancji przez skórę może być tak samo istotne, jak przy narażeniu drogą oddechową); „Muta. 1B” (działanie mutagenne na komórki rozrodcze kategorii zagrożenia 1B). Jako biomarkery zawodowego narażenia na benzen zaproponowano stężenie benzenu 2,5 μg/l moczu oraz stężenie kwasu S-fenylomerkapturowego (S-PMA) na poziomie 9,0 μg/g kreatyniny w moczu. Zakres tematyczny artykułu obejmuje zagadnienia zdrowia oraz bezpieczeństwa i higieny środowiska pracy będące przedmiotem badań z zakresu nauk o zdrowiu i inżynierii środowiska.
... 10,139 Numerous studies have reported that benzene exposure induced leukemia-related chromosomal changes that are commonly observed in AML can be detected in the peripheral blood lymphocytes of workers who have been heavily exposed to benzene. 11,12,140,141 The presence of monosomy 5 and monosomy 7 has been observed in the human lymphocytes from healthy workers exposed to benzene. 140 Benzene metabolites also produce AML-related chromosomal changes in human CD34 þ progenitor cells, providing evidence that chromosomal aberrations, such as aneuploidy and translocations, may be the genetic pathway for induction of AML by benzene. ...
... 11,12,140,141 The presence of monosomy 5 and monosomy 7 has been observed in the human lymphocytes from healthy workers exposed to benzene. 140 Benzene metabolites also produce AML-related chromosomal changes in human CD34 þ progenitor cells, providing evidence that chromosomal aberrations, such as aneuploidy and translocations, may be the genetic pathway for induction of AML by benzene. 141,142 Furthermore, a study using OctoChrome fluorescent in situ hybridization and the micronucleus-centromere assay reported that benzene exposure causes monosomy of chromosomes 5, 6, 7, and 10 and trisomy of chromosomes 8, 9, 17, 21, and 22. 143 Chromosomal aberrations such as translocation t (14;18) and dose-dependent induction of long-arm deletion of chromosome 6 [del(6q)] have been reported in workers who have been exposed to benzene. ...
Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.
... Chronic exposure to certain chemicals such as benzene, embalming fluids, ethylene oxides, and herbicides also appears to be at increased risk [28]. Workers exposed to benzene were found to have increased levels of cytogenetic abnormalities associated with AML [29]. Fig. 2 showed that the highest number was M4 10 (33.3%) patients, followed by M1 7(23.3%), ...
... [27] It has been attributed to variety of factors that include: monomer contraction during polymerization; air entrapment during mixing; monomer vaporization associated with exothermic reaction; presence of residual monomer; inadequate pressure on the flask and processing temperature higher than 74 C. [28,29] It has been declared that 11% porosity in acrylic resin is linked to poor esthetic and reduction in mechanical properties. ...
... [32] Several factors have contributed to porosity that includes; polymerization method, thickness and the material of chose, air entrapment during mixing; monomer vaporization associated with exothermic reaction and presence of residual monomer. [28,29] Porosity in a material considered unfavourable condition that can weaken the denture and cause high internal stress which result in a greater vulnerability to distortion. ...
The present work focuses on the upper Cretaceous (Cenomanian-early Campanian) carbonate successions in selected wells from northwestern Iraq. These successions are represented by Gir Bir (Cenomanian-early Turonian), Wajna (late Santonian) and Mushorah (early Campanian) Formations. The succession has affected by early burial near-surface, unconformity-related and deep burial diagenesis represented by cementation, neomorphism, dolomitization, dedolomitization, silicification, authigenesis of glauconite and pyrite, compaction, micritization, solution and porosity formation. The common porosity types are intergranular, fenestral, intercrystalline, moldic, vuggy, channel and fracture. Three porosity zones (I, II, and III) are identified depending on variation in gamma ray which reflects their shale content. The upper part of zone (II) is highly porous and regarded on the main reservoir unit in the middle and upper parts of the Gir Bir Formation. Fracture and moldic and vuggy dissolution features in addition to karstic and fissure features are responsible for the porosity increase in the fractured reservoir unit.
... Chronic exposure to certain chemicals such as benzene, embalming fluids, ethylene oxides, and herbicides also appears to be at increased risk [28]. Workers exposed to benzene were found to have increased levels of cytogenetic abnormalities associated with AML [29]. Smoking has been increased risk of developing AML especially in those persons aged 60-75 [30]. ...
... [27] It has been attributed to variety of factors that include: monomer contraction during polymerization; air entrapment during mixing; monomer vaporization associated with exothermic reaction; presence of residual monomer; inadequate pressure on the flask and processing temperature higher than 74 C. [28,29] It has been declared that 11% porosity in acrylic resin is linked to poor esthetic and reduction in mechanical properties. ...
... The saline agent will provide a better bond between particles and acrylic [41] and minimizes agglomeration. [17,30] In order to reduce agglomeration of NPs, they were added to acrylic monomer first and then mixed with powder [23,25,29] with aid of probe sonicator (Biosafer 900-02) using the settings provided below: Sonication was started with 8s on and 3s off to keep the temperature within the set range. ...
... Chronic exposure to certain chemicals such as benzene, embalming fluids, ethylene oxides, and herbicides also appears to be at increased risk [28]. Workers exposed to benzene were found to have increased levels of cytogenetic abnormalities associated with AML [29]. Smoking has been increased risk of developing AML Fig.1 shows the passivity of AML case to some CD markers by flow cytometry. ...
This study has been carried out in Erbil City -Iraq, 30 patients were diagnosis by flow cytometry as AML which they were admitted to Nanakaly Hospital for Blood Disease and submitted to chemotherapy. Number of adults/children 22 (73.3%) / 8 (26.7%), female / male 13 (43.3%) / 17(56.7%). Only 20 (66.7%) patients were smoker. The highest number was subtyping M4 10 (33.3%) patients, followed by M1 7(23.3%), M3 6(20%), M2 were 3(10%) patients. M5 and M6 were 2 (6.7%). Ten candida spp isolates before induction phase chemotherapy show 9(90%) C.albicans, 1(10%) C. lusitaniae, and from 32 isolates after induction phase chemotherapy, 17(53.1%) C.albicans, 7(21.9%) C. lusitaniae, and 8(25%) C.famata. According to the site of infection, before starting chemotherapy 8(88.9%) C. albicans isolates were in the oral cavity and 1(11.1%) on the skin, while C. lusitaniae was 1 (100%) in oral cavity only. While after chemotherapy 12(70.6%) C.albicans in the oral cavity and 5(29.4%) on the skin, C. lusitaniae was 2 (28.6%) in the oral cavity and 5(71.4%) on the skin, while all C. famata was 8 (100%) on the skin The immunophenotype shows that the number and percentage of patients which the myeloid cells expressed cyMPO was 27(90) with mean percentage of positivity 59.38, while all patients expressed CD33 and CD13 on their blast cell 30(100) with a mean percentage of positivity 59.81 and 30.83 respectively.
... In turn, pBQ, as with chemotherapeutic alkylating agents, acts as an electrophile on DNA within the target cell inducing myelotoxicity (Irons 1985a;Irons et al. 1992). Additional support for this hypothesis was evidenced by abnormalities in chromosome 5 and 7 in lymphocytes of healthy benzene-exposed workers, and in reports of abnormalities in chromosome 5 and 7 human CD34þ hematopoietic progenitor cells following in vitro exposure to benzene metabolites (Irons and Stillman 1996;Zhang et al. 1998;Stillman et al. 1999Stillman et al. , 2000Smith et al. 2000). However, abnormalities in chromosomes 5 and 7 have not been directly correlated concurrently in the bone marrow (e.g. the target organ of toxicity) of diseased workers following exposure to benzene. ...
The Shanghai Health Study (SHS) was a large epidemiology study conducted as a joint effort between the University of Colorado and Fudan University in Shanghai, China. The study was funded by members of the American Petroleum Institute between 2001 and 2009 and was designed to evaluate the human health effects associated with benzene exposure. Two arms of the SHS included: an occupational-based molecular epidemiology study and several hospital-based case control studies. Consistent with historical literature, following sufficient exposure to relatively high airborne concentrations and years of exposure, the SHS concluded that exposure to benzene resulted in an increased risk of various blood and bone marrow abnormalities such as benzene poisoning, aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Non-Hodgkin lymphoma (NHL) was not significantly increased for the exposures examined in this study. Perhaps the most important contribution of the SHS was furthering our understanding of the mechanism of benzene-induced bone marrow toxicity and the importance of identifying the proper subset of MDS relevant to benzene. Investigators found that benzene-exposed workers exhibited bone marrow morphology consistent with an immune-mediated inflammatory response. Contrary to historic reports, no consistent pattern of cytogenetic abnormalities was identified in these workers. Taken together, findings from SHS provided evidence that the mechanism for benzene-induced bone marrow damage was not initiated by chromosome abnormalities. Instead, chronic inflammation, followed by an immune-mediated response, is likely to play a more significant role in benzene-induced disease initiation and progression than previously thought.
... Third, myeloid precursors produce large amounts of enzymes that can both generate cytotoxic mediators as part of their normal function (e.g. myeloperoxidase), but can also activate environmental chemicals able to interact with cells, producing genotoxic intermediates [37], linked to the formation of chromosome rearrangements typical of leukemia, such as benzene and its derivatives [38,39]. ...
... Table 3 describes frequencies of cytogenetic abnormalities and prognostic IPSS-R risk category in MDS [7,18]. Furthermore, in addition to prognostic value, cytogenetic analysis has a pivotal role in confirming or in ruling out the diagnosis of MDS, when hematological findings Losses of part or all of chromosomes 5 and 7 and complex chromosome aberrations are particularly common in the oligoblastic myelogenous leukemias (and the overt leukemias) associated with prior treatment with cytotoxic drugs, radiation, or exposure to benzene [19]. Categories of cytogenetic abnormalities correlated with median survival have been determined. ...
Myelodisplastic syndromes (MDS) are heterogeneous myeloid disorders characterized by peripheral cytopenias and increased risk of transformation into acute myelogenous leukemia (AML). MDS are generally suspected in the presence of cytopenia on routine analysis and the evaluation of bone marrow cells morphology and cellularity leads to correct diagnosis of MDS. The incidence of MDS is approximately five cases per 100,000 people per year in the general population, but it increases up to 50 cases per 100,000 people per year after 60 years of age. Typically MDS affect the elderly, with a median age at diagnosis of 65-70 years. Here the current therapeutic approaches for MDS are evaluated by searching the PubMed database. Establishing the prognosis in MDS patients is a key element of therapy. In fact an accurate estimate of prognosis drives decisions about the choice and timing of the therapeutic options. Therapy is selected based on prognostic risk assessment, cytogenetic pattern, transfusion needs and biological characteristics of the disease, comorbidities and clinical condition of the patients. In lower-risk patients the goals of therapy are different from those in higher-risk patients. In lower-risk patients, the aim of therapy is to reduce transfusion needs and transformation to higher risk disease or AML, improving the quality of life and survival. In higher-risk patients, the main goal of therapy is to prolong survival and to reduce the risk of AML transformation. Current therapies include growth factor support, lenalidomide, immunomodulatory and hypomethylating agents, intensive chemotherapy, and allogenic stem cell transplantation. The challenge when dealing with MDS patients is to select the optimal treatment by balancing efficacy and toxicity.
... Previously, we and others reported that aneuploidy, a numerical chromosome aberration and form of genomic instability [Sheltzer et al., 2011;Solomon et al., 2011] that has been associated with leukemogenesis [Schoch and Haferlach, 2002], was induced in the mature blood cells of workers occupationally exposed to benzene Zhang et al., 1998;Zhang et al., 2011] and FA [Orsiere et al., 2006]. We also detected aneuploidy in the circulating myeloid progenitor cells of workers exposed to benzene and FA [Zhang et al., 2010b;Lan et al., 2015]. ...
Benzene and formaldehyde (FA) are important industrial chemicals and environmental pollutants that cause leukemia by inducing DNA damage and chromosome aberrations in hematopoietic stem cells (HSC), the target cells for leukemia. Our previous studies showed that workers exposed to benzene and FA exhibit increased levels of aneuploidy in their blood cells. As centrosome amplification is a common phenomenon in human cancers, including leukemia, and is associated with aneuploidy in carcinogenesis, we hypothesized that benzene and FA would induce centrosome amplification in vitro. We treated human lymphoblastoid TK6 cells with a range of concentrations of hydroquinone (HQ, a benzene metabolite) or FA for 24 h, allowed the cells to recover in fresh medium for 24 h, and examined centrosome amplification; chromosomal gain, loss, and breakage; and cytotoxicity. We included melphalan and etoposide, chemotherapeutic drugs that cause therapy-related acute myeloid leukemia and that have been shown to induce centrosome amplification as well as chromosomal aneuploidy and breakage, as positive controls. Melphalan and etoposide induced centrosome amplification and chromosome gain and breakage in a dose-dependent manner, at cytotoxic concentrations. HQ, though cytotoxic, did not induce centrosome amplification or any chromosomal aberration. FA-induced centrosome amplification and cytotoxicity, but did not induce chromosomal aberrations. Our data suggest, for the first time, that centrosome amplification is a potential mechanism underlying FA-induced leukemogenesis, but not benzene-induced leukemogenesis, as mediated through HQ. Future studies are needed to delineate the mechanisms of centrosome amplification and its association with DNA damage, chromosomal aneuploidy and carcinogenesis, following exposure to FA. Environ. Mol. Mutagen., 2015. © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.
... Regarding the position of chromosome breakage, it was mostly found in chromosome number 3 and 6, while the study by Zhang, et al 18,19 reported that anomaly were more frequent in chromosome number 5, 7, and 9, while Sasiadek and Jagielski 20 found anomaly in chromosome number 2, 4, 6, and 9. From the gene cards of the Institute of Gene International, it is known that some diseases are related to the number of chromosome damage. 21 It is mentioned that abnormalities/diseases might occur if there is damage to the chromosome numbers 3, 6, 7, and 9. Damage to chromosomes number 3 is associated with metabolism disorders, and anomaly in chromosome 3 is more closely related to triglycerides/HDL ratio, especially for the Caucasian families in USA, 22 and increasing of the heart problems and metabolic syndrome. ...
Background: Benzene has been used in industry since long time and its level in environment should be controled. Although environmental benzene level has been controlled to less than 1 ppm, negative effect of benzene exposure is still observed, such as chromosome breakage. This study aimed to know the prevalence of lymphocyte chromosome breakage and the influencing factors among workers in low level benzene exposure.Methods: This was a cross sectional study in oil & gas industry T, conducted between September 2007 and April 2010. The study subjects consisted of 115 workers from production section and head office. Data on type of work, duration of benzene exposure, and antioxidant consumption were collected by interview as well as observation of working process. Lymphocyte chromosome breakage was examined by banding method. Analysis of relationship between chromosome breakage and risk factors was performed by chi-square and odd ratio, whereas the role of determinant risk factors was analyzed by multivariate forward stepwise.Results: Overall lymphocyte chromosome breakage was experieced by 72 out of 115 subjects (62.61%). The prevalence among workers at production section was 68.9%, while among administration workers was 40% (p > 0.05). Low antioxidant intake increases the risk of chromosome breakage (p = 0.035; ORadjusted = 2.90; 95%CI 1.08-7.78). Other influencing factors are: type of work (p = 0,10; ORcrude = 3.32; 95% CI 1.33-8.3) and chronic benzene exposure at workplace (p = 0.014; ORcrude = 2.61; 95% CI 1.2-5.67), while the work practice-behavior decreases the lymphocyte chromosome breakage (p = 0.007; ORadjusted = 0.30; 95% CI 0.15-0.76).Conclusion: The prevalence of lymphocyte chromosome breakage in the environment with low benzene exposure is quite high especially in production workers. Chronic benzene exposure in the workplace, type of work, and low antioxidant consumption is related to lymphocyte chromosome breakage. Thus, benzene in the workplace should be controlled to less than 1 ppm, and the habit of high antioxidant consumption is recommended.
