Abstract:
:Differential CYP1A1 inducibility, reflecting variations in aromatic hydrocarbon receptor (AHR) affinity among inbred mouse strains, is an important determinant of environmental toxicity. We took advantage of the Ahr polymorphism in C57BL/6 and DBA/2 mice to develop an oligonucleotide-hybridization screening approach for the rapid identification of DNA sequence differences between Ahr alleles. Oligonucleotides containing single-base changes at polymorphic sites were immobilized on a solid support and hybridized with C57BL/6 or DBA/2 AHR cDNA radiolabeled probes. The observed hybridization patterns demonstrate that this approach can be used to detect nucleotide differences in the Ahr coding region with very high accuracy. In parallel experiments, we used a yeast two-hybrid system to assess phenotypic differences in AHR function. AHR activation, as measured by beta-galactosidase reporter activity in Saccharomyces cerevisiae strain SFY526, was determined following treatment with varying doses of the AHR ligand beta-naphthoflavone (BNF). We found that the C57BL/6 AHR has about a 15-fold higher affinity for BNF than the DBA/2 AHR, in much better agreement with results reported for whole-animal studies than the values observed by in vitro ligand-binding assays. Using C57BL/6 and DBA/2 AHR chimeric proteins, we also confirmed the previously reported observation that an A375V change is principally responsible for the high- to low-affinity AHR phenotype. There has been no straightforward method to reliably and reproducibly phenotype large numbers of humans for CYP1A1 inducibility or AHR affinity. Screening human AHR cDNAs by oligonucleotide-hybridization and yeast two-hybrid methodologies will be invaluable for the rapid and unequivocal determination of changes in DNA sequence and receptor-ligand affinities associated with human AHR polymorphisms.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Maier A,Micka J,Miller K,Denko T,Chang CY,Nebert DW,Alvaro Pugadoi
10.1289/ehp.106-1533118subject
Has Abstractpub_date
1998-07-01 00:00:00pages
421-6issue
7eissn
0091-6765issn
1552-9924journal_volume
106pub_type
杂志文章abstract::N-Substituted aromatic compounds can be metabolized in most species to N-acetylated derivatives that are themselves subject to further enzymatic transformations, including hydrolysis and N,O-acyltransfer. These proceses can either potentiate or ameliorate the biological responses to these N-substituted derivatives. De...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.834943
更新日期:1983-03-01 00:00:00
abstract::Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate nickel compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 t...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s369
更新日期:1994-09-01 00:00:00
abstract::The reported incidence of acute respiratory illness in families exposed to different concentrations of air pollution was studied during two consecutive school years. The purpose of the study was to determine the effect of increased exposure to sulfur dioxide and suspended particulate matter. In each of four study comm...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8244165
更新日期:1982-04-01 00:00:00
abstract::Biomarkers are desirable for quantitating human exposure to environmental tobacco smoke (ETS) and for predicting potential health risks for exposed individuals. A number of biomarkers of ETS have been proposed. At present cotinine, measured in blood, saliva, or urine, appears to be the most specific and the most sensi...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.99107s2349
更新日期:1999-05-01 00:00:00
abstract::Ethene is, on a molar basis, a major urban air pollutant. It has been shown beyond doubt that a fraction of inhaled ethene is metabolized in mammals (including humans) via ethylene oxide, an electrophilic reagent that has been shown to be mutagenic and carcinogenic. To the extent that the linearity hypothesis for dose...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.102-1566931
更新日期:1994-10-01 00:00:00
abstract::The 11 September 2001 terrorist attack on New York City's World Trade Center (WTC) caused an unprecedented environmental emergency. The collapse of the towers sent a tremendous cloud of crushed building materials and other pollutants into the air of lower Manhattan. In response to the calamity, federal, state, and cit...
journal_title:Environmental health perspectives
pub_type: 评论,杂志文章
doi:10.1289/ehp.111-1241533
更新日期:2003-06-01 00:00:00
abstract::This paper concerns the testing for Hardy-Weinberg equilibrium and the estimation of gene frequency in the human leukocyte antigens (HLA) system. An extensive simulation study for both testing and estimation is given for investigating the performance of the projection method by Eguchi and Matsuura, which has a closed ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9087149
更新日期:1990-07-01 00:00:00
abstract::The Lower North Shore region of the St. Lawrence River is home to a fish-eating population that displays an unusually high body burden of several organochlorines, including polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLCs). We measured biomarkers indicative of liver enzyme induction and investigated th...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7970
更新日期:2005-10-01 00:00:00
abstract::Virginia Bioinformatics Institute, in conjunction with National Institutes of Environmental Health Sciences, hosted a conference, "Toxicogenomics through the Eyes of Informatics," in Bethesda, Maryland, USA, on 12-13 May 2003. Researchers around the world met to discuss how the application of bioinformatics tools, met...
journal_title:Environmental health perspectives
pub_type:
doi:10.1289/ehp.112-1241996
更新日期:2004-05-01 00:00:00
abstract::The distribution of inhaled mineral fibers in the lung determines the site and severity of disease caused by the fibers. Some of our recent work has described the fate of inhaled asbestos fibers in rodents. After a brief inhalation exposure, asbestos fibers are deposited primarily at the first alveolar duct bifurcatio...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.94102s5197
更新日期:1994-10-01 00:00:00
abstract::Fumonisin B1(FB1) is a fungal metabolite of Fusarium verticillioides (= F. moniliforme), a fungus that grows on many crops worldwide. Previous studies demonstrated that male BD IX rats consuming diets containing 50 ppm fumonisin B1 developed hepatocellular carcinomas. In our recent studies, diets containing FB1 at 50 ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.01109s2309
更新日期:2001-05-01 00:00:00
abstract::In different weather conditions, constituents and concentrations of pollutants, personal exposure, and biologic responses to air pollution may vary. In this study we assessed the effects of four air pollutants on mortality in both cool and warm seasons in Hong Kong, a subtropical city. Daily counts of mortality, due t...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.01109335
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND:Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB. OBJECTIVES:In the present study we examined the ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1408126
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:In male rodents, anogenital distance (AGD) provides a sensitive and continuous correlate of androgen exposure in the intrauterine environment and predicts later reproductive success. Some endocrine-disrupting chemicals can alter male reproductive tract development, including shortening AGD, in both rodents a...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1103421
更新日期:2011-07-01 00:00:00
abstract::The many anatomical, physiological, and biochemical differences among various mammalian species make it difficult to extrapolate carcinogenic potency data from animals to humans. The process is further complicated by the multistep origin of most malignant tumors in animals and humans due to the interaction of target c...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.887773
更新日期:1988-04-01 00:00:00
abstract::This subject concerns the complex interrelationship of a genetically determined protein deficiency, enzymes which are inhibited by that protein, environmental challenges such as cigarette smoke and industrial pollutants, and the occurrence of obstructive lung disease (Fig. 1). Unequivocal establishment of an etiologic...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.792957
更新日期:1979-04-01 00:00:00
abstract::A few animal studies on the possible carcinogenic effect of magnetic fields have been published. They have been designed to reveal a possible tumor promotion obtained by applying continuous or pulsed alternating fields at flux densities varying between 0.5 microT and 30 mT on mice or rats initiated with different init...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.95103s263
更新日期:1995-03-01 00:00:00
abstract::Germ-line mutations of the mouse have for years comprised one class of biological markers for mammalian reproductive and developmental toxicology. Understanding the molecular nature of mutations and the mechanisms by which mutations are translated into specific (and often complex) phenotypes, however, still looms as a...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.877441
更新日期:1987-10-01 00:00:00
abstract:BACKGROUND:Environmental exposures to phthalates, particularly high-molecular-weight (HMW) phthalates, are suspected to contribute to allergy. OBJECTIVE:We assessed whether phthalate metabolites are associated with allergic symptoms and sensitization in a large nationally representative sample. METHODS:We used data o...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1206211
更新日期:2013-10-01 00:00:00
abstract::Although para-nonylphenol (NP) is known as an endocrine disruptor, the immunologic effect of NP has been poorly analyzed. We found that NP from 5 to 50 microM caused a dose-dependent stimulatory effect on the generation of reactive oxygen species (ROS) in human blood neutrophils, which was measured by using a chemilum...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.6584
更新日期:2004-04-01 00:00:00
abstract::Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.9088149
更新日期:1990-08-01 00:00:00
abstract:OBJECTIVE:The goal of this study was to identify mental, behavioral, and cognitive disorders that may be triggered or exacerbated during heat waves, predisposing individuals to heat-related morbidity and mortality. DESIGN:Using health outcome data from Adelaide, South Australia, for 1993-2006, we estimated the effect ...
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
abstract::Scaling of the quantified dispositional parameters of xenobiotics from animals to man is of interest from the standpoint of toxicology (e.g., poisoning and risk assessment). Scaling is also important from the standpoint of therapeutics because it represents a strategy for predicting first-use-in-human doses in clinica...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.96104400
更新日期:1996-04-01 00:00:00
abstract::We present a pilot study of individuals (liquidators) who were engaged in clean-up operations after the disaster at the nuclear power plant at Chernobyl in Ukraine. In the 10 years since the disaster, adverse health effects among exposed individuals have not been clearly defined. There is widespread fear of damage to ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.97105s61445
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND:Experimental tools for studying the complex steroidogenic interactions that occur between placenta and fetus during human pregnancy are extremely limited. OBJECTIVES:We aimed to develop a co-culture model to study steroidogenesis by the human fetoplacental unit and its disruption by exposure to environmenta...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1307518
更新日期:2014-04-01 00:00:00
abstract::We report on findings from a 2-year follow-up study of immigrants originating from exposed areas around the site of the 1986 Chernobyl accident matched with comparison subjects emigrating from other republics in the Confederation of Independent States. In the initial study of 708 immigrants, the samples were matched b...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.97105s61545
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND:Benchmark dose (BMD) modeling is an important step in human health risk assessment and is used as the default approach to identify the point of departure for risk assessment. A probabilistic framework for dose-response assessment has been proposed and advocated by various institutions and organizations; ther...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP1289
更新日期:2018-01-11 00:00:00
abstract::Chromate is an established human carcinogen. There have been many studies of the reactivity of chromate aimed at improving understanding of chromate toxicity. In the present paper a number of conclusions of these studies are reviewed and considered in the light of new results obtained in our laboratories. A number of ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s33
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND:The potential impact of microwave radiofrequency electromagnetic fields (RF-EMF) emitted by wireless communication devices on neurocognitive functions of adolescents is controversial. In a previous analysis, we found changes in figural memory scores associated with a higher cumulative RF-EMF brain dose in ad...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP2427
更新日期:2018-07-23 00:00:00
abstract::Alzheimer's disease is a progressive degenerative brain disease of unknown etiology, characterized by the development of large numbers of neurofibrillary tangles and senile plaques in the brain. Aluminum salts may be used experimentally to produce lesions which are similar, but not identical, to the neurofibrillary ta...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8563149
更新日期:1985-11-01 00:00:00