Using Lichen Chemistry to Assess Airborne Tungsten and Cobalt in Fallon, Nevada

This paper describes the use of lichen chemistry to assess airborne tungsten and cobalt in Fallon, Nevada, where a cluster of childhood leukemia has been on going since 1997. Lichens and their rock substrates were collected from Rattlesnake Hill within Fallon as well as from four different rock outcrops located north, east, south, and west of Fallon and at least 20 km away from the town center. In the lichens themselves, W and Co are significantly higher within Fallon than in the combined control site outside of Fallon. In the rock substrates of the lichens, no differences exist in W and Co. The W and Co differences in lichens cannot be attributed to substrate geochemistry. Fallon is distinctive in west central Nevada for high airborne W and Co, and given its cluster of childhood leukemia, it stands to reason that additional biomedical research is in order to test directly the leukogenicity of combined airborne W and Co.     

Spatial patterns of tungsten and cobalt in surface dust of Fallon,Nevada

Spatial patterns of tungsten and cobalt are described for surface dust of Fallon, Nevada, where a cluster of childhood leukemia has been ongoing since 1997. In earlier research, airborne tungsten and cobalt was shown to be elevated in total suspended particulates in Fallon. To fine-tune the spatial patterns of tungsten and cobalt deposition in Fallon, surface dust was collected in a grid pattern within as well as outside of Fallon to establish background concentrations of metals. In surface dust, tungsten and cobalt show sharp peaks (934 ppm and 98 ppm, respectively) within Fallon just north of highway 50 and west of highway 95. These two peaks overlap spatially, and given the grid pattern used for collecting surface dust, the source area of these two airborne metals can be pinpointed to the vicinity of hard-metal industry located north of highway 50 and west of highway 95. Fallon is distinctive in west central Nevada because of high airborne tungsten and cobalt particulates, and given its cluster of childhood leukemia, it stands to reason that additional biomedical research is in order to test directly the leukogenicity of combined airborne tungsten and cobalt particulates.     

Review: Windows of exposure to pesticides for increased risk of childhood leukemia

Leukemia is the leading cause of cancer resulting in mortality of children, and there is some evidence suggesting the increased incidence rate increasing during the recent decades. Limited human evidence indicates an increased risk of developing leukemia in childhood as a result of pesticide exposure, with possible significance of exposure occurring during the developmental periods including preconception, pregnancy, and childhood. This review examines the results of relevant literature on the timing of pesticide exposure and leukemia diagnosed in childhood. Results suggest that the risk from pesticide exposure seems to be greater during pregnancy. Other findings indicate that maternal occupational exposure may be more of a greater concern than the paternal occupational exposure; and that the residential indoor use of pesticides tends to result in higher risk estimates than the residential outdoor use. Only limited data are available on particular pesticides, genetic factors, critical windows of exposure during development, and their association with different histological types of leukemia.     

甲醛对小鼠造血调控相关转录因子在mRNA水平表达的影响

为了研究甲醛污染毒性的分子机制,探究了气态甲醛暴露对小鼠造血调控相关转录因子在mRNA水平表达产生的影响.实验将18只雄性Balb/C小鼠随机分为3组,每组6只,采用仿真式口鼻吸入方法暴露于不同浓度(0.5 mg·m-3和3.0 mg·m-3)的气态甲醛环境中,每天8 h,为期2周.染毒结束后,分别进行血细胞分析和RT-PCR测定小鼠骨髓相关髓系转录因子、红系和巨核系转录因子、淋巴系转录因子在mRNA水平的表达量.结果发现,与对照组相比,相关转录因子C/EBPα、SCL、GATA-2、c-myb、GATA-1及淋巴系转录因子在mRNA水平表达量随甲醛浓度的升高受到不同程度的影响,部分具有统计学差异(p0.05).其中,转录因子C/EBPα、SCL及GATA-2在mRNA水平表达量随甲醛浓度的升高而降低,而转录因子c-myb、GATA-1及淋巴系转录因子Ikzf5、PAX5在mRNA水平表达量随甲醛浓度的升高而升高.研究表明,高浓度甲醛暴露会影响小鼠骨髓造血调控相关转录因子的正常表达.     

甲醛致骨髓造血细胞遗传毒性研究展望

甲醛是我国目前最主要的室内空气污染物.相当一部分新装修的房屋室内甲醛浓度超过安全标准,室内甲醛污染已成为中国的环境污染公害.2004年6月15日世界卫生组织下属的国际癌症研究局确认甲醛是人类致癌物,然而甲醛是否能导致人类白血病?该公报指出:虽然有流行病学的证据,但是由于致病机制并不清楚,需要做进一步的研究,才能得出结论.问题的关键是:甲醛或其衍生成分经血液向骨髓转移的分子机制,以及这些成分在骨髓中对微环境组分的作用机制.     

Studies on Formation of Liquid and Gaseous Formaldehyde-Induced DNA-Protein Crosslinks in Rat Marrow Cells

甲醛是一种遗传毒物,流行病学研究表明甲醛可能具有诱导白血病的作用,然而甲醛诱导白血病的机制目前还不清楚. 以不同浓度液态和气态甲醛对大鼠骨髓细胞进行染毒,采用KCl-SDS 法检测了骨髓细胞 DNA-蛋白质交联程度,并采用单细胞凝胶电泳技术(彗星实验)检测了骨髓细胞 DNA 链断裂程度. 研究结果表明:与对照组相比,低浓度甲醛(液态甲醛浓度为:5μmol·L-1和25μmol·L-1;气态甲醛浓度为:0.5mg·m-3 和 1.0mg·m-3)可以引起 DNA断裂水平显著增高 (p<0.01);而高浓度甲醛 (液态甲醛浓度为:125μmol·L-1 和 625μmol·L-1;气态甲醛浓度为:3.0mg·m-3)则可以引起 DNA-蛋白质交联水平显著增高(p<0.01; p<0.05). 研究结果提示:甲醛染毒可以导致大鼠骨髓细胞DNA的损伤,暗示甲醛诱导白血病具有高度的可能性.     

Systematic review and meta-analysis of glyphosate exposure and risk of lymphohematopoietic cancers

This systematic review and meta-analysis rigorously examines the relationship between glyphosate exposure and risk of lymphohematopoietic cancer (LHC) including NHL, Hodgkin lymphoma (HL), multiple myeloma (MM), and leukemia. Meta-relative risks (meta-RRs) were positive and marginally statistically significant for the association between any versus no use of glyphosate and risk of NHL (meta-RR = 1.3, 95% confidence interval (CI) = 1.0–1.6, based on six studies) and MM (meta-RR = 1.4, 95% CI = 1.0–1.9; four studies). Associations were statistically null for HL (meta-RR = 1.1, 95% CI = 0.7–1.6; two studies), leukemia (meta-RR = 1.0, 95% CI = 0.6–1.5; three studies), and NHL subtypes except B-cell lymphoma (two studies each). Bias and confounding may account for observed associations. Meta-analysis is constrained by few studies and a crude exposure metric, while the overall body of literature is methodologically limited and findings are not strong or consistent. Thus, a causal relationship has not been established between glyphosate exposure and risk of any type of LHC.     

4-(4-(Methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one: a novel COX-2 inhibitor acting selectively and directly on cancerous B-lymphocyte mitochondria

A new series of 3-phenoxyazetidin-2-ones (β-lactams) were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In this study, the effects of a synthetic of β-lactam-structured COX-2 inhibitor with 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one on cell viability of cancerous lymphoblast isolated from patients diagnosed with acute lymphocytic leukemia (ALL) and normal lymphocytes collected from healthy donors were investigated. The viability % of cancer lymphoblast and normal lymphocyte treated 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one were tested with MTT assay. Apoptosis and necrosis were measured by double stains of annexin V and propidium iodide, and caspase-3 as a final mediator in apoptotic death measured by colorimetric assay. Mitochondria were isolated from both cancerous lymphoblast and normal lymphocytes to measure parameters of mitochondrial damage such as reactive oxygen species (ROS) formation, mitochondrial membrane potential decrease, swelling, and cytochrome c release following the administration of azithidine-2-one derivative, 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one. Our results showed that 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one inhibited proliferation of cancerous lymphoblast in a concentration-dependent manner by inducing apoptosis but not in normal lymphocytes. Treatment with azithidine-2-one derivative produced a rapid loss of mitochondrial transmembrane potential, stimulation of release of ROS and mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Data suggest that 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one-induced ROS production led to mitochondria-mediated death signaling that resulted in apoptosis in cancerous lymphoblast cells. The induction of apoptosis by azithidine-2-one compounds, such as 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one, may provide a mechanism for its cancer chemopreventive action in acute lymphocytic leukemia cells.     

Assessing health risk from benzene pollution in an urban area

A health hazard, specifically the leukaemia risk, is evaluatedfrom different sources of benzene exposure with relation to apopulation living in an urban area of Italy. The population exposure is calculated for a reference year by sexand lyfestyle, with respect to smokers and non smokers. Potentialhealth risk is therefore quantified by means of mathematicalmodels and the relative significance of the different sources is described. The results of the analysis are useful for the identification ofappropriate risk reduction strategies to minimize exposure, inparticular when resulting from lifestyle and personal activities.