Abstract:
BACKGROUND:Organophosphate developmental neurotoxicity involves multiple mechanisms converging on neural cell replication and differentiation. OBJECTIVES:We evaluated mechanisms contributing to the adverse effects of chlorpyrifos (CPF) on DNA synthesis, cell number and size, and cell signaling mediated by adenylyl cyclase (AC) in PC12 cells, a neuronotypic cell line that recapitulates the essential features of developing mammalian neurons. RESULTS:In undifferentiated cells, cholinergic receptor antagonists had little or no protective effect against the antimitotic actions of CPF; however, when nerve growth factor was used to evoke differentiation, the antagonists showed partial protection against deficits in cell loss and alteration in cell size elicited by CPF, but were ineffective in preventing the deterioration of AC signaling. Nicotine, which stimulates nicotinic acetylcholine receptors but also possesses a mixture of prooxidant/antioxidant activity, had adverse effects by itself but also protected undifferentiated cells from the actions of CPF and had mixed additive/protective effects on cell number in differentiating cells. The antioxidant vitamin E also protected both undifferentiated and differentiating cells from many of the adverse effects of CPF but worsened the impact on AC signaling. Theophylline, which prevents the breakdown of cyclic AMP, was the only agent that restored AC signaling to normal or supranormal levels but did so at further cost to cell replication. CONCLUSIONS:Our results show definitive contributions of cholinergic hyperstimulation, oxidative stress, and interference with AC signaling in the developmental neurotoxicity of CPF and point to the potential use of this information to design treatments to ameliorate these adverse effects.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Slotkin TA,MacKillop EA,Ryde IT,Seidler FJdoi
10.1289/ehp.10194subject
Has Abstractpub_date
2007-09-01 00:00:00pages
1306-13issue
9eissn
0091-6765issn
1552-9924journal_volume
115pub_type
杂志文章abstract:OBJECTIVE:Animal feeding practices in the United States have changed considerably over the past century. As large-scale, concentrated production methods have become the predominant model for animal husbandry, animal feeds have been modified to include ingredients ranging from rendered animals and animal waste to antibi...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.9760
更新日期:2007-05-01 00:00:00
abstract::Lung burden analysis was performed on 126 autopsy cases of persons who died in New York City from 1966 through 1968. Of the 126 cases, 107 were probably non-occupationally exposed, judging by occupational history and asbestos body content of lung. Fifty-three of the 107 cases contained short chrysotile fibers/fibrils,...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s5235
更新日期:1994-10-01 00:00:00
abstract::This article summarizes the basic facts about the measurement of ionizing radiation, usually referred to as radiation dosimetry. The article defines the common radiation quantities and units; gives typical levels of natural radiation and medical exposures; and describes the most important biological effects of radiati...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.919145
更新日期:1991-02-01 00:00:00
abstract::Environmental pollution with the nephrotoxic metal cadmium is considered a potential health risk for the general population. In 1976 it was reported that the cadmium concentration in human kidney cortex in Sweden had increased in parallel with increasing levels in soil and grain during the twentieth century. Since the...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106175
更新日期:1998-04-01 00:00:00
abstract::The use of physiologically based pharmacokinetic (PBPK) models has been proposed as a means of estimating the dose of the reactive metabolites of carcinogenic xenobiotics reaching target tissues, thereby affording an opportunity to base estimates of potential cancer risk on tissue dose rather than external levels of e...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.94102s1137
更新日期:1994-12-01 00:00:00
abstract::High-performance liquid chromatography (HPLC) methods are described which permit the rapid isolation of multiple target macromolecules from the tissues of animals exposed to chemical mutagens. DNA and selected chromosomal proteins are isolated in a simple two step separation scheme. Isolated nuclei are dissolved in 3 ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.856273
更新日期:1985-10-01 00:00:00
abstract:BACKGROUND:Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.11378
更新日期:2009-01-01 00:00:00
abstract::Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment ap...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.97105s3655
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND:The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. OBJECTIVE:In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS:We studied a cohort of 158 asthmatic and 50 nonasthmatic sch...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.10926
更新日期:2008-06-01 00:00:00
abstract::Nicotine and cigarette smoke extract show acute physiological effects: increasing tracheal pressure (PTR), pulmonary artery pressure (PPA), systemic blood pressure (PSYST), and left atrium pressure (PLA); and decreasing cardiac output (QAORTA) and blood flow to the left lower lobe (QLLL). In addition, cigarette smokin...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.8772283
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND:Understanding the potential links between extreme weather events and human health in India is important in the context of vulnerability and adaptation to climate change. Research exploring such linkages in India is sparse. OBJECTIVES:We evaluated the association between extreme precipitation and gastrointes...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1306807
更新日期:2014-03-01 00:00:00
abstract::We extended our previous analyses of term low birth weight (LBW) and preterm birth to 1994-2000, a period of declining air pollution levels in the South Coast Air Basin. We speculated that the effects we observed previously for carbon monoxide, particulate matter < 10 microm in aerodynamic diameter (PM10), and traffic...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7751
更新日期:2005-09-01 00:00:00
abstract::Southwest metropolitan Mexico City (SWMMC) inhabitants have been exposed several hours per day for the last 6 years to photochemical smog, ozone being the most important oxidant pollutant. Subjects exposed to the SWMMC atmosphere develop several histopathological changes in their nasal mucosa: dysplasia is the most si...
journal_title:Environmental health perspectives
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1289/ehp.101-1519752
更新日期:1993-06-01 00:00:00
abstract::Traditional models of toxicity have relied on dissecting chemical action into pharmacokinetic and pharmacodynamic processes. However, the integration of genomic information with toxicology will enhance our basic understanding of these processes and significantly change the way we apply toxicological information to ris...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.02110s6919
更新日期:2002-12-01 00:00:00
abstract::Direct studies of the function of a given cell type often require that the cell type be obtained in pure culture. A number of different specific metabolic activities have been attributed to pulmonary endothelial cells, yet with few exceptions the conclusions were based on indirect evidence. Thus, to improve our abilit...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8035171
更新日期:1980-04-01 00:00:00
abstract::The methylation of specific cytosine residues in DNA has been implicated in regulating gene expression and facilitating functional specialization of cellular phenotypes. Generally, the demethylation of certain CpG sites correlates with transcriptional activation of genes. 5-Azacytidine is an inhibitor of DNA methylati...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8980189
更新日期:1989-03-01 00:00:00
abstract::We analyzed data from 798 lead workers to determine whether polymorphisms in the genes encoding delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR) were associated with or modified relations of lead exposure and dose measures with renal outcomes. Lea...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.6116
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:Previous literature suggests an association between organochlorines and behavioral measures in childhood, including inattention. OBJECTIVE:This study was designed to assess whether prenatal organochlorine exposure is associated with measures of attention in early infancy. METHODS:We investigated an associa...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.10553
更新日期:2008-05-01 00:00:00
abstract::The chlorinated hydrocarbons chloroform (CHCl3), 1,1-dichlorethane (1,1-DCE) and 1,2-dichloroethane (1,2-DCE) have been detected in finished drinking water. When administered to B6C3F1 mice by gavage in corn oil, these compounds have been shown to induce hepatic tumors. The present study examines the effect on liver t...
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
abstract::As part of a cohort study of the effects of chronic exposure to lead on pregnancy outcome and child development, lead concentrations in the umbilical cord and placental tissues (body and membranes) from 9 late fetal deaths, 23 preterm births, and 18 births associated with premature rupture of the amniotic membranes we...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.90-1519491
更新日期:1991-01-01 00:00:00
abstract::Studies performed earlier have shown a positive relation between blood lead (a parameter for lead body burden) and blood pressure, whereas such a relation between urine cadmium (a parameter for cadmium body burden) and blood pressure could not be shown. Median (i.e., 50th percentile, P50) blood levels in the general p...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.887867
更新日期:1988-06-01 00:00:00
abstract::The study reported here presents the results of an investigation of a marsh-cove ecosystem heavily contaminated by cadmium. The most contaminated aquatic sediments were dredged in 1972-73, but the resuspension of the sediments and recycle of water from the dredge spoil resulted in reestablishment of a large contaminat...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.792867
更新日期:1979-02-01 00:00:00
abstract::A brief review of the literature indicates that nutritional deficiencies have been shown to increase the absorption and toxicity of orally ingested lead and cadmium. Results from recent studies indicates that low level oral ingestion of cadmium and lead perturbs the metabolism of zinc, copper, and iron and that these ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7825141
更新日期:1978-08-01 00:00:00
abstract::Minority populations face a wide variety of economic, institutional, and cultural barriers to health care. These barriers and low levels of education and income pose significant challenges for health professionals in developing cancer research and prevention-control strategies. It is suggested that specific segments o...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.95103s8287
更新日期:1995-11-01 00:00:00
abstract::Pregnant rats were exposed by inhalation to vapor concentrations of 100, 200, 400 or 800 ppm of ethylene glycol monopropyl ether acetate on days 6 through 15 of gestation. Concentrations of 400 and 800 ppm reduced the feed intake, mean body weight and red blood cell counts. Mean corpuscular volume and mean corpuscular...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.845725
更新日期:1984-08-01 00:00:00
abstract:BACKGROUND:Endocrine-disrupting chemicals have been shown to have broad effects on development, but their mutagenic actions that can lead to cancer have been less clearly demonstrated. Physiological levels of estrogen have been shown to stimulate DNA damage in breast epithelial cells through mechanisms mediated by estr...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP5221
更新日期:2020-01-01 00:00:00
abstract::In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrin...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.97105s51121
更新日期:1997-09-01 00:00:00
abstract::Diffuse pulmonary fibrosis is associated with bleomycin administration to humans. The sequential reactions of lung cells to this drug have now been investigated in mice following injection of 20 mg/kg bleomycin twice per week for 4 to 8 weeks. Cytoplasmic and subendothelial edema was first observed in large vessels an...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7616119
更新日期:1976-08-01 00:00:00
abstract::The central feature of hemopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The entry into cell cycle of the dormant stem cells may be promoted by such factors as interleukin-1, interleukin-6 (IL-6), and gra...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.8980199
更新日期:1989-03-01 00:00:00
abstract::The past and current EPA research and regulatory programs as they relate to non-regulated emissions from light-duty motor vehicles are reviewed. Provisions of Sections 202(a) and 211 of the 1970 Clean Air Act Amendments are discussed and their relationships to the nonregulated emissions issue detailed. The EPA positio...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.75105
更新日期:1975-04-01 00:00:00