Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Production usage and potential occupational exposure to benzene are described in this review, as are selected, relevant reports presenting evidence evidence implicating benzene as a causative factor in leukemia, particularly acute myelogenous leukemia, pancytopenia (including aplastic anemia) and chromosomal aberrations. A chronologic account of events in the 1970s in the United States, largely based on epidemiologic evdince collected and prepared by the National Institute for Occupational Safety and Health, caused the regulatory agency, the Department of Labor, through its Occupational Safety and Health Administration to declare benzene a human leukemogen and carcinogen and to publish an emergency temporary standard of 1 ppm in May, 1977, but this standard has not been legalized.
 ...
PMID:Benzene--attempts to establish a lower exposure standard in the United States. A review. 35 61

The distribution of various types of leukemia due to chronic exposure to benzene is described in a series comprising 34 cases. The incidence of leukemia among 31 show-workers was 13.5/100,000. Acute myeloblastic leukemia was the most frequent type, followed by preleukemia, acute erythroleukemia and acute lymphoblastic leukemia. The extreme rarity of chronic myeloid leukemia was a noteworthy finding. The differences and similarities between the distribution of various types of leukemia in different series of patients with chronic exposure to benzene and ionizing radiation are discussed.
 ...
PMID:Types of leukemia in chronic benzene poisoning. A study in thirty-four patients. 81 44

The association between occupational and other environmental exposures was evaluated in 60 acute myelogenous leukemia cases and controls. Odds ratios and 95% confidence intervals for prior cytotoxic therapy and benzene exposure, adjusted for age, sex, and race by logistic regression, were 3.7 (0.7, 19.9) and 2.6 (0.4, 15.2), respectively. No other work-related associations, including employment in electrical occupations, were present. Other associations were suggestive but may have been due to biases in control selection or small numbers of subjects. The risks for prior cytotoxic therapy (odds ratio = 10.2) and benzene exposure (odds ratio = 11.4) were concentrated in 13 patients with French-American-British M4 leukemia; no environmental exposures were associated with French-American-British subtypes M1 and M2. These findings support the concept that French-American-British histological subtypes of AML may have different etiologies.
 ...
PMID:Is histological subtype a marker for environmental exposures in acute myelogenous leukemia? 130 3

The effects of in vitro pretreatment with benzene metabolites on colony-forming response of murine bone marrow cells stimulated with recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) were examined. Pretreatment with hydroquinone (HQ) at concentrations ranging from picomolar to micromolar for 30 min resulted in a 1.5- to 4.6-fold enhancement in colonies formed in response to rGM-CSF that was due to an increase in granulocyte/macrophage colonies. The synergism equaled or exceeded that reported for the effects of interleukin 1, interleukin 3, or interleukin 6 with GM-CSF. Optimal enhancement was obtained with 1 microM HQ and was largely independent of the concentration of rGM-CSF. Pretreatment with other authentic benzene metabolites, phenol and catechol, and the putative metabolite trans, trans-muconaldehyde did not enhance growth factor response. Coadministration of phenol and HQ did not enhance the maximal rGM-CSF response obtained with HQ alone but shifted the optimal concentration to 100 pM. Synergism between HQ and rGM-CSF was observed with nonadherent bone marrow cells and lineage-depleted bone marrow cells, suggesting an intrinsic effect on recruitment of myeloid progenitor cells not normally responsive to rGM-CSF. Alterations in differentiation in a myeloid progenitor cell population may be of relevance in the pathogenesis of acute myelogenous leukemia secondary to drug or chemical exposure.
 ...
PMID:Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colony-stimulating factor in vitro. 157 Feb 88

The findings of the studies summarized in this report provide some understanding of the possible role of dosimetry in the different response of the rats and mice to benzene in the long-term bioassay studies. The more sensitive species, the mice, definitely has a higher capacity to metabolize benzene and to metabolize it to more of the putative toxic metabolites than do rats. A major finding of these studies is that in three different animal species, from mice to monkeys, the metabolic pathways leading to production of the putative toxic metabolites appear to be low-capacity, high-affinity pathways that are saturated at relatively low-exposure concentrations. This does not prove, but suggests, that the same may be true in humans. If the total formation of the putative toxic metabolites is predictive of the toxicity of benzene, then the animal studies suggest that calculations of the risk associated with low dose exposures based on the results of animal studies conducted at high doses would underestimate the toxicity of benzene. The current report concerns only dosimetry. Another problem in assessing the risk to humans from benzene exposure is the fact that the animal models do not respond to benzene in the same way as humans. The major concern for humans exposed to benzene, based on epidemiology studies, is the risk of developing acute myelogenous leukemia (Rinksy, 1987). The cancers developed by the rodents on the long-term bioassay studies were at other sites (liver, lung, Zymbal's gland, lymph tissue, ovaries, and mammary gland). There is as yet no good animal model for benzene-induced leukemia. However, it has been suggested that benzene may also increase the incidence of Hodgkin's disease, malignant lymphoma, multiple myeloma and lung cancer in humans, although a statistical basis for this is lacking (Askoy, 1985). It is not unreasonable to assume that whatever form of cancer is induced, the induction is most likely through the reactive metabolites produced from benzene. Therefore, the dosimetry of these metabolites is pertinent. Our studies indicate that benzene metabolite dosimetry data obtained in animals provides data relevant to the estimation of human risks.
 ...
PMID:Benzene dosimetry in experimental animals: relevance for risk assessment. 162 Jul 20

Chronic exposure of humans to benzene has been shown to have a cytotoxic effect on hematopoietic progenitor cells in intermediate stages of differentiation, which can lead to aplastic anemia and acute myelogenous leukemia. We studied the effect of hydroquinone (HQ), a toxic metabolite of benzene found in the bone marrow, on the human promyelocytic leukemia cell line (HL-60), which can be induced to differentiate to both monocyte and myeloid cells, and thus has been used as a surrogate for a granulocyte/macrophage progenitor cell. Exposure of HL-60 cells to noncytotoxic concentrations of HQ for 3 hours before induction with phorbol myristate acetate (TPA) caused a dose-dependent inhibition of the acquisition of characteristics of monocytic differentiation, such as adherence, nonspecific esterase (NSE) activity, and phagocytosis, but had no effect on cell proliferation. HQ appeared to be affecting maturation beyond the monoblast/promonocyte stages. HQ also prevented differentiation induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]; however, the block occurred after the acquisition of adherence. HQ at concentrations that inhibited monocytic differentiation had no effect on differentiation to granulocytes, suggesting that the block in the differentiation of these bipotential cells is a step unique to the monocytic pathway. HQ was unable to prevent differentiation induced by the macrophage-derived cytokine, interleukin (IL)-1, a differentiation factor for cells of the monocytic lineage.
 ...
PMID:Induced differentiation of HL-60 promyelocytic leukemia cells to monocyte/macrophages is inhibited by hydroquinone, a hematotoxic metabolite of benzene. 173 8

Epidemiological studies indicating that exposure to organic solvents is a risk factor for haematological malignancies are reviewed. Exposure to benzene is a risk factor for ANLL. A preleukaemic phase with pancytopenia is common and may be associated with a normo- or hypercellular marrow with morphological characteristics suggesting MDS. There are indications that other organic solvents than benzene may be leukaemogenic. Certain chromosome aberrations are characteristic in leukaemic cells from solvent exposed ANLL patients. The average latency time from start of occupational exposure until diagnosis is about 10-11 years. There is epidemiological evidence that exposure to organic solvents may also increase the risk of lymphoproliferative malignancies, i.e. ALL, NHL, HD and myeloma.
 ...
PMID:Exposure to organic solvents and risk of haematological malignancies. 173 76

Occupational exposure to benzene, a major industrial chemical, has been associated with various blood dyscrasias and increased incidence of acute myelogenous leukemia in humans. It is established that benzene requires metabolism to induce its effects. Benzene exposure in humans and animals has also been shown to result in structural and numerical chromosomal aberrations in lymphocytes and bone marrow cells, indicating that benzene is genotoxic. In this review we have attempted to compile the available evidence on the role of increased free radical activity in benzene-induced myelotoxic and leukemogenic effects. Benzene administration to rodents has been associated with increased lipid peroxidation in liver, plasma, and bone marrow, as shown by an increase in the formation of thiobarbituric-acid reactive products that absorb at 535 nm. Benzene administration to rodents also results in increased prostaglandin levels indicating increased arachidonic acid peroxidation. Other evidence includes the fact that bone marrow cells and their microsomal fractions isolated from rodents following benzene-treatment have a higher capacity to form oxygen free radicals. The bone marrow contains several peroxidases, the most prevalent of which is myeloperoxidase. The peroxidatic metabolism of the benzene metabolites, phenol and hydroquinone, results in arachidonic acid peroxidation and oxygen activation to superoxide radicals, respectively. These metabolites, upon co-administration also produce a myelotoxicity similar to that observed with benzene. Recently, we have found that exposure of human promyelocytic leukemia (HL-60) cells (a cell line rich in myeloperoxidase), to the benzene metabolites, hydroquinone and 1,2,4-benzenetriol results in increased steady-state levels of 8-hydroxydeoxyguanosine a marker of oxidative DNA damage. Peroxidatic metabolism of benzene's phenolic metabolites may therefore be responsible for the increased free radical activity and toxicity produced by benzene in bone marrow. We thus hypothesize that free radicals contribute, at least in part, to the toxic and leukemogenic effects of benzene.
 ...
PMID:Potential role of free radicals in benzene-induced myelotoxicity and leukemia. 176 8

Because chronic benzene exposure is associated with acute myeloblastic leukemia and other myeloproliferative disorders, we sought to determine whether short-term benzene exposure provides a growth advantage for granulopoietic elements over erythropoietic elements. Groups of male DBA/2J mice were exposed to 0, 10, 30, or 100 ppm benzene (6 h/day for 5 days). One day and 5 days after the benzene exposures, the numbers of the two most primitive erythroid progenitor cells (BFU-E and CFU-E) and the numbers of the most primitive granulocytic progenitor cells (GM-CFU-C) were assessed. Additional groups of mice were given hemolytic doses of phenylhydrazine (PHZ) during the 5 days of benzene exposure, while other groups of mice were given PHZ during the 5 days of recovery from benzene exposure. These experiments were designed to determine the effects of benzene exposure on progenitor cell numbers during periods of markedly heightened erythropoiesis. The results demonstrate that short-term benzene exposure does induce a growth advantage for granulocytic cells in both the bone marrow and spleen of exposed mice. Moreover, a benzene-induced shift toward granulopoiesis is observed even in those mice treated with a powerful erythropoietic stimulus. These effects disappear 5 days after cessation of benzene exposure in the bone marrow but persist in the spleen of mice treated with phenylhydrazine.
 ...
PMID:Short term benzene exposure provides a growth advantage for granulopoietic progenitor cells over erythroid progenitor cells. 207 27

This paper examines recent risk assessments for benzene and observes a number of inconsistencies within the study and consistencies between studies that should effect the quantitative determination of the risk from benzene exposure. Comparisons across studies show that only acute myeloid leukemia (AML) is found to be consistently in excess with significant benzene exposure. The data from the Pliofilm study that forms the basis of most quantitative assessments reveal that all the AML cases came from only one of the three studied plants and that all the benzene exposure data came from the other plants. Hematological data from the 1940s from the plant from which almost all of the industrial hygiene exposure data come do not correlate well with the originally published exposure estimates but do correlate well with an alternative set of exposure estimates that are much greater than those estimates originally published. Temporal relationships within the study are not consistent with those of other studies. The dose-response relationship is strongly nonlinear. Other data suggest that the leukemogenic effect of benzene is nonlinear and may derive from a threshold toxicity.
 ...
PMID:Consistencies and inconsistencies underlying the quantitative assessment of leukemia risk from benzene exposure. 204 Feb 46


1 2 3 4 5 6 7 8 9 10 Next >>