Abstract:
:The role of cell-specific metabolism in benzene toxicity was examined in both murine and human bone marrow. Hemopoietic progenitor cells and stromal cells are important control points for regulation of hemopoiesis. We show that the selective toxicity of hydroquinone at the level of the macrophage in murine bone marrow stroma may be explained by a high peroxidase/nicotanimide adenine dinucleotide phosphate, reduced [NAD(P)H]:quinone oxidoreductase (NQO1) ratio. Peroxidases metabolize hydroquinone to the reactive 1,4-benzoquinone, whereas NQO1 reduces the quinones formed, resulting in detoxification. Peroxidase and NQO1 activity in human stromal cultures vary as a function of time in culture, with peroxidase activity decreasing and NQO1 activity increasing with time. Peroxidase activity and, more specifically, myeloperoxidase, which had previously been considered to be expressed at the promyelocyte level, was detected in murine lineage-negative and human CD34+ progenitor cells. This provides a metabolic mechanism whereby phenolic metabolites of benzene can be bioactivated in progenitor cells, which are considered initial target cells for the development of leukemias. Consequences of a high peroxidase/NQO1 ratio in HL-60 cells were shown to include hydroquinone-induced apoptosis. Hydroquinone can also inhibit proteases known to play a role in induction of apoptosis, suggesting that it may be able to inhibit apoptosis induced by other stimuli. Modulation of apoptosis may lead to aberrant hemopoiesis and neoplastic progression. This enzyme-directed approach has identified target cells of the phenolic metabolites of benzene in bone marrow and provided a metabolic basis for benzene-induced toxicity at the level of the progenitor cell in both murine and human bone marrow.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Ross D,Siegel D,Schattenberg DG,Sun XM,Moran JLdoi
10.1289/ehp.961041177subject
Has Abstractpub_date
1996-12-01 00:00:00pages
1177-82eissn
0091-6765issn
1552-9924journal_volume
104 Suppl 6pub_type
杂志文章abstract::We measured tumor-associated proteins (TAPs) and pollutants in blood, serum, and urine of 200 nonsmoking women 50-65 years of age, residing in the rural municipality of Peer or in Hoboken or Wilrijk, industrial suburbs of Antwerp, Belgium. Persons with occupational exposures or commuting to other towns were excluded. ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8811
更新日期:2006-06-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.10917
更新日期:2008-07-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.94102s321
更新日期:1994-09-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1307277
更新日期:2014-06-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.11339
更新日期:2008-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP167
更新日期:2016-09-01 00:00:00
abstract::This report updates the risk assessment by Crump and Allen for benzene-induced leukemia that was based on a cohort exposed to benzene in the manufacture of Pliofilm. The present study derives new risk estimates using data from follow-up through 1987 (whereas the earlier assessment only had follow-up available through ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.961041437
更新日期:1996-12-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1104051
更新日期:2012-04-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9087233
更新日期:1990-07-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s515
更新日期:1994-10-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP6470
更新日期:2020-09-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.97105294
更新日期:1997-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9196101
更新日期:1991-12-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.93101s663
更新日期:1993-12-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8142127
更新日期:1981-12-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8454171
更新日期:1984-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.951031136
更新日期:1995-12-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/EHP483
更新日期:2017-06-13 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.866989
更新日期:1986-11-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.02110s4573
更新日期:2002-08-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0901003
更新日期:2010-03-01 00:00:00
abstract::The occurrence of high cadmium levels in the digestive gland (hepatopancreas) of the crab Cancer pagurus is reviewed and its possible significance to human health is discussed. Previous attempts to isolate this cadmium in its native form are briefly reviewed and the present method used in this laboratory to isolate cr...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8665101
更新日期:1986-03-01 00:00:00
abstract:INTRODUCTION:Prenatal exposure to some pesticides can adversely affect male reproductive health in animals. We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children. DESIGN:Within a prospective birth cohort, we perfo...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8741
更新日期:2006-07-01 00:00:00
abstract:BACKGROUND:We have previously shown that adult male mice exposure to low doses of an ubiquitous endocrine disruptor, di(2-ethylhexyl) phthalate (DEHP), alters courtship behavior. OBJECTIVE:The effects of adult exposure to low doses of DEHP alone or in an environmental phthalate mixture on estrous cyclicity, reproducti...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP7662
更新日期:2021-01-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106s51213
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND:Diethylstilbestrol (DES) is a synthetic estrogen associated with adverse effects on reproductive organs. DES-induced toxicity of the mouse seminal vesicle (SV) is mediated by estrogen receptor α (ERα), which alters expression of seminal vesicle secretory protein IV (Svs4) and lactoferrin (Ltf) genes. OBJECT...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1307351
更新日期:2014-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106739
更新日期:1998-11-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1104018
更新日期:2011-11-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP2129
更新日期:2018-04-06 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.96104s2173
更新日期:1996-04-01 00:00:00