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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic exposure of humans to benzene (BZ), a widely used industrial chemical and a ubiquitous environmental pollutant, causes aplastic anemia and acute myeloid leukemia. The purpose of the studies reported here was to determine whether the observed depression of bone marrow (BM) cellularity in mice administered benzene was reflected in a suppression of development of all of the hematopoietic lineages and to confirm the ability of interleukin-1 alpha (IL-1 alpha) to prevent BZ-induced BM cell depression. We report that BZ, administered twice per day for 2 days to C57B1/6J mice at a dose of 600 mg/kg body weight, caused a significant depression of the total number of nucleated BM cells per femur when measured on day 3. The observed depression reflects a complex situation that represents the net effect of a decrease in the total number of cells of the lymphocytic and erythroid lineages, along with an increase in the number of intermediate and terminally differentiated cells of the granulocytic lineage. An experiment to monitor the effects of BZ over a 7-day period showed a progressive depressive effect on the lymphocytes and an initial depression of the erythroid cells at day 3 that remained constant until day 7. Conversely, the numbers of intermediate and terminally differentiated granulocytes progressively increased over the 7 days. The BM appeared to recover from the depressive effects of BZ immediately upon cessation of exposure, as the number of nucleated BM cells began to rise by day 5 and was equal to that of the control group by day 7. The results expand our earlier finding (Renz and Kalf 1991) that the overall depression of BM cellularity occurs because of an inability of the stromal fibroblast to produce colony-stimulating factors essential for stem and progenitor cell survival. This results from inhibition by the BZ metabolite, hydroquinone (HQ), of the processing of pre-IL-1 alpha to the mature cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A morphological analysis of the short-term effects of benzene on the development of the hematological cells in the bone marrow of mice and the effects of interleukin-1 alpha on the process. 771 69

Although the relationship between benzene and acute nonlymphocytic leukemia (ANLL) is well established, most of the analytic cohort investigations examining the relationship between benzene and hematologic neoplasms have evaluated only death certificates to validate diagnoses. In a follow-up study of 74,828 benzene-exposed and 35,805 non-exposed workers in China, pathology reports, medical records, and/or histopathologic material were reviewed for all patients with hematopoietic malignancies to ensure correct classification and to provide clinicopathologic descriptions. Eighty-two patients with hematopoietic neoplasms and related disorders were identified among benzene-exposed workers, including 32 cases of acute leukemia, 7--myelodysplastic syndrome (MDS), 9--chronic granulocytic leukemia (CGL), 20--malignant lymphoma or related disorder (ML), 9--aplastic anemia, and 5 others. Among the comparison group, 13 hematologic malignancies were observed, including 6 patients with acute leukemia, 2--CGL, 3--ML, and 2 others. The hematopathologic characteristics of the benzene-exposed ANLL cases resembled those following chemotherapy or radiotherapy. ANLL in workers exposed to benzene may represent a distinct clinicopathologic entity, with characteristics similar to treatment-related ANLL, including a preceding preleukemic phase in some patients. Results in our series, one of the largest to data, also indicate that a greater diversity of hematologic neoplasms is evident among benzene-exposed workers than previously described.
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PMID:Hematopoietic malignancies and related disorders among benzene-exposed workers in China. 792 Feb 31

Although benzene is best known as a compound that causes bone marrow depression leading to aplastic anemia in animals and humans, it also induces acute myelogenous leukemia in humans. The epidemiological evidence for leukemogenesis in humans is contrasted with the results of animal bioassays. This review focuses on several of the problems that face those investigators attempting to unravel the mechanism of benzene-induced leukemogenesis. Benzene metabolism is reviewed with the aim of suggesting metabolites that may play a role in the etiology of the disease. The data relating to the formation of DNA adducts and their potential significance are analyzed. The clastogenic activity of benzene is discussed both in terms of biomarkers of exposure and as a potential indication of leukemogenesis. In addition to chromosome aberrations, sister chromatid exchange, and micronucleus formation, the significance of chromosomal translocations is discussed. The mutagenic activity of benzene metabolites is reviewed and benzene is placed in perspective as a leukemogen with other carcinogens and the lack of leukemogenic activity by compounds of related structure is noted. Finally, a pathway from exposure to benzene to eventual leukemia is discussed in terms of biochemical mechanisms, the role of cytokines and related factors, latency, and expression of leukemia.
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PMID:A perspective on benzene leukemogenesis. 794 90

Four new or updated epidemiologic studies were presented at a meeting on the health effects of gasoline exposure held in Miami, Florida, November 5-8, 1991. A focus of these studies was whether there is a relationship between gasoline exposure and kidney cancer and leukemia. For gasoline distribution workers, who have a relatively high exposure, there was some evidence for a kidney cancer relationship in three studies but none in the fourth. There was evidence for an acute myelocytic leukemia relationship in three studies. The fourth study dealt only with kidney cancer. It is possible that the benzene content of gasoline was responsible for the leukemia findings. It is uncertain whether gasoline exposure is a cause of kidney cancer.
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PMID:Review of new evidence regarding the relationship of gasoline exposure to kidney cancer and leukemia. 802 Apr 32

Acute and chronic exposure to benzene vapors poses a number of health hazards to humans. To evaluate the probability that a specific degree of exposure will produce an adverse effect, risk assessment methods must be used. This paper reviews much of the published information and evaluates the various risk assessments for benzene that have been conducted over the past 20 years. There is sufficient evidence that chronic exposure to relatively high concentrations of benzene can produce an increased incidence of acute myelogenous leukemia (AML). Some studies have indicated that benzene may cause other leukemias, but due to the inconsistency of results, the evidence is not conclusive. To predict the leukemogenic risk for humans exposed to much lower doses of benzene than those observed in most epidemiology studies, a model must be used. Although several models could yield plausible results, to date most risk assessments have used the linear-quadratic or conditional logistic models. These appear to be the most appropriate ones for providing the cancer risk for airborne concentrations of 1 ppb to 10 ppm, the range most often observed in the community and workplace. Of the seven major epidemiology studies that have been conducted, there is a consensus that the Pliofilm cohort (rubber workers) is the best one for estimating the cancer potency because it is the only one with good exposure and incidence of disease data. The current EPA, OSHA, and ACGIH cancer potency estimates for benzene are based largely on this cohort. A retrospective exposure assessment and an analysis of the incidence of disease in these workers were completed in 1991. All of these issues are discussed and the implications evaluated in this paper. The range of benzene exposures to which Americans are commonly exposed and the current regulatory criteria are also presented.
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PMID:Benzene toxicity and risk assessment, 1972-1992: implications for future regulation. 802 Apr 42

Chronic exposure of humans to benzene (BZ) affects hematopoietic progenitor cells in intermediate stages of differentiation which can lead to aplastic anemia and/or acute myelogenous leukemia and some of its variant forms. We studied the effects of BZ and hydroquinone (HQ), a toxic bone marrow metabolite, on the human HL-60 promyelocytic leukemic cell line. Because the HL-60 cell is bipotential and can be induced to differentiate to monocytes or granulocytes it has been used in many studies as a surrogate for the granulocyte/macrophage committed cell, GM-CFU. Treatment of HL-60 cells with BZ specifically induced differentiation along the granulocytic lineage as measured by morphology, induction of superoxide production and chloroacetate esterase activity and the appearance of the L12-2 surface antigen. Differentiation was induced via the activation of protein kinase C and the phosphorylation of several proteins known to be involved in HL-60 cell differentiation. Subsequent to kinase C activation, arachidonic acid was released from membrane phospholipids and the 5-lipoxygenase pathway was activated for the production of leukotriene D4 (LTD4) required for granulocytic differentiation. BZ induction of granulopoiesis was prevented by preincubation of HL-60 cells with inhibitors of protein kinase C, 5-lipoxygenase, gamma-glutamyl transpeptidase required for the conversion of LTC4 to LTD4, or LTD4 receptor antagonists. Treatment of HL-60 cells with tetraphorbol myristate acetate (TPA), 1 alpha, 25-dihydroxyvitamin D3 (1,25-(OH2)D3) or interleukin-1 (IL-1) induced HL-60 cells to differentiate to monocytes/macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of benzene and hydroquinone on myeloid differentiation of HL-60 promyelocytic leukemia cells. 812 4

Occupational exposure to low-frequency electromagnetic fields (EMF) was studied in 250 leukemia patients and 261 brain-tumor cases, diagnosed in 1983-87 and compared with a control group of 1,121 randomly selected men, from the mid-region of Sweden, 1983-87. We based the exposure assessment on measurements from 1,015 different workplaces. On the basis of the job held longest during the 10-year period before diagnosis, we found an association between the average, daily, mean level of EMF and chronic lymphocytic leukemia (CLL). The risk increased with increasing level of exposure. The odds ratios (OR) and the 95 percent confidence interval (CI) for three consecutive levels of exposure were: 1.1 (CI = 0.5-2.3); 2.2 (CI = 1.1-4.3); 3.0 (CI = 1.6-5.8), respectively. No association was observed for acute myeloid leukemia (OR = 1.0, CI = 0.5-1.8; OR = 0.8, CI = 0.4-1.6; OR = 1.0, CI = 0.6-1.9). For brain tumors, the corresponding risk estimates were 1.0 (CI = 0.7-1.6); 1.5 (CI = 1.0-2.2); 1.4 (CI = 0.9-2.1). Different EMF indices were tested. Tasks with frequent or large variations between high and low field-densities (high standard deviation) were more common among CLL subjects. For brain tumors, a prolonged high level (high median values) showed the strongest association. Confounding by place of residence, smoking, benzene, ionizing radiation, pesticides, and solvents was evaluated, and these factors did not seem to have a decisive influence on the associations. We also analyzed other potential sources of bias. For CLL, there were indications of an excess number of low-exposure subjects among non-responders, which, to some extent, may have enhanced but not caused the risk estimates obtained. Our conclusion is that the study supports the hypothesis that occupational EMF exposure is a hazard in the development of certain cancers.
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PMID:Occupational exposure to electromagnetic fields in relation to leukemia and brain tumors: a case-control study in Sweden. 821 79

The risk of acute myeloid leukemia (AML) within different occupations was studied, using occupational information obtained from the Swedish 1970 census. Follow-up in the Swedish Cancer Register was carried out from 1971 to 1984. Among male petrol station attendants, 10 cases were observed versus 2.8 expected (observed/expected = 3.6, 95% confidence interval 1.7-6.6). For several decades, Swedish petrol has contained 3-5% of benzene. Thus, a hypothesis was that benzene had contributed to the excess risk. The work histories of the 10 cases were reconstructed through interviews with surviving relatives and were compatible with the hypothesis. However, because the air benzene exposures at petrol stations always have been lower than benzene exposures associated previously with an increased risk of AML, the leukemogenic effect of benzene may have been potentiated by other petrol or vehicle exhaust components.
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PMID:Acute myeloid leukemia among petrol station attendants. 901 30

Until recently, cALL has been uncommon in sub-Saharan Africa, but there is now emerging a peak of incidence at the age 3 to 5 years in west and southern Africa. Prognosis for African patients with cALL is poor because of a multitude of clinical, biological and social factors. AML is seen at high frequency (probably indicating truly high incidence) in male children 5-14 years, of whom up to a quarter present with chloroma. It is predicted that the incidence of AML in adults may rise in the near future, related to cigarette smoking, occupational and environmental exposures to benzene and other pollutants, and the prescription of alkylating agents to young people with malignant disease. CML shows no particular epidemiological features, except for a high frequency in young adults and children, reflecting the age structure of the whole population. There are two forms of B-CLL: one is seen most commonly in women of low socioeconomic status towards the end of the their reproductive life, and is probably related to an initially polyclonal expansion of B-cells in response of recurrent malaria and other infections; the other is seen over the age of 45 years, with men being affected twice as commonly as women, as in the western world.
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PMID:Leukaemias in Africa. 836 Dec 19

Epidemiological studies have shown an association between cigarette smoking and increased risk of myeloid leukemia in smokers. In evaluating this link it is important to note that cigarette smoke contains benzene, among other carcinogens. Since chronic benzene, among other carcinogens. Since chronic benzene exposure causes acute myeloid leukemia in humans, we aimed to determine the uptake and metabolic activation of benzene from cigarette smoke in smokers by measuring the levels of the urinary benzene metabolite, trans,trans-muconic acid (t,t-MA). The method used involved a clean-up procedure, followed by high-performance liquid chromatography with UV detection. The levels of urinary t,t-MA ranged from 0.02 to 1.3 mg/g creatinine, resulting in a mean of 0.29 +/- 0.04 mg/g creatinine in 42 male smokers, and corresponding values in nonsmokers ranged from "nondetectable" to 0.52 mg/g creatinine with an average of 0.09 +/- 0.02 mg/g creatinine. In the current study, the levels of t,t-MA in smokers were about 3 times higher than those in nonsmokers (P = 0.0001), and a significant correlation between concentration of t,t-MA and levels of cotinine in smokers was observed (r = 0.55; P = 0.0001; 95% confidence interval, 0.30-0.93), suggesting that urinary t,t-MA can be utilized as a biochemical marker to quantitate benzene exposure due to cigarette smoking.
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PMID:Urinary trans,trans-muconic acid as an indicator of exposure to benzene in cigarette smokers. 842 Jun 12


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