Abstract:
:Previously we have demonstrated that several xenobiotics can induce multidrug (mdr) gene expression in cultures of primary isolated hepatocytes. One of the best of these xenobiotic inducers in rat hepatocytes is 2-acetylaminofluorene (2-AAF), which induces mdr expression by an enhancement of mdr gene transcription. In all species studied to date, AAF is extensively and variously metabolized. In this study we have sought to determine if AAF per se or a metabolite is responsible for mediating the increase in mdr gene transcription and expression. This study demonstrates that AAF per se is not active, but that the effect of AAF we have observed on mdr gene transcription and expression in the rat is due to the formation of a reactive metabolite(s). Our data indicate that this reactive metabolite is probably N-acetoxy-2-aminofluorene or the sulfate ester of N-hydroxy-AAF. The requirement for the formation of one of these metabolites may explain the differences in species response to AAF, in terms of mdr gene expression, that we have observed. We hypothesize that the mechanism by which mdr gene transcription is increased in response to AAF involves a covalent interaction between a reactive metabolite and an mdr gene regulatory protein. Our current work is concerned with the exploration of this hypothesis.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Gant TW,Schrenk D,Silverman JA,Thorgeirsson SSdoi
10.1289/ehp.94102s6209subject
Has Abstractpub_date
1994-10-01 00:00:00pages
209-12eissn
0091-6765issn
1552-9924journal_volume
102 Suppl 6pub_type
杂志文章abstract::Although press reports indicate that the leakage of methyl isocyanate (MIC) on December 3, 1984, in Bhopal has led to an increase in spontaneous abortions, stillbirths, infant mortality, and fetal abnormalities, no clinical or experimental studies on the reproductive toxicity of MIC were reported in scientific journal...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8772153
更新日期:1987-06-01 00:00:00
abstract:BACKGROUND:Millions of people worldwide consume arsenic-contaminated rice; however, little is known about the uptake and bioavailability of arsenic species after arsenic-contaminated rice ingestion. OBJECTIVES:In this study, we assessed arsenic speciation in greenhouse-grown and supermarket-bought rice, and determined...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9322
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:Controversy remains regarding the relationship between ambient ozone and mortality worldwide. In mainland China, the largest developing country, there has been no prior study investigating the acute effect of O3 on death risk. Given the changes in types of air pollution from conventional coal combustion to t...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9014
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:There is a need to identify and evaluate an effective mitigation program for arsenic exposure from drinking water in Bangladesh. OBJECTIVE:We evaluated the effectiveness of a multifaceted mitigation program to reduce As exposure among 11,746 individuals in a prospective cohort study initiated in 2000 in Ara...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9833
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND:Phthalates, known endocrine disruptors, may play a role in breast carcinogenesis. Few studies have examined phthalates in relation to breast cancer (BC), and, to our knowledge, none have considered survival following BC. OBJECTIVES:We examined 11 urinary phthalate metabolites, individually and as molar sum ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP2083
更新日期:2018-04-26 00:00:00
abstract::In this study, the cohort consisted of 18,135 distribution employees with potential exposure to gasoline for at least one year at land-based terminals (n = 9,026) or on marine vessels (n = 9,109) between 1946 and 1985. The primary objective of the study was to determine the relationship, if any, between exposure to ga...
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
abstract::Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phospholipase A2 (PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.85-1568329
更新日期:1990-04-01 00:00:00
abstract:BACKGROUND:Air pollution exposure increases cardiovascular morbidity and mortality and is a major global public health concern. OBJECTIVES:We investigated the benefits of reducing personal exposure to urban air pollution in patients with coronary heart disease. METHODS:In an open randomized crossover trial, 98 patien...
journal_title:Environmental health perspectives
pub_type: 杂志文章,随机对照试验
doi:10.1289/ehp.1103898
更新日期:2012-03-01 00:00:00
abstract::The historical exposures to aromatic amines of various occupational groups are briefly reviewed. Modern studies indicate that other occupational groups might have risks worth investigating; these include machinists and workers in the chemical industry. Details of a recent investigation into the exposure of dye workers...
journal_title:Environmental health perspectives
pub_type: 历史文章,杂志文章
doi:10.1289/ehp.834913
更新日期:1983-03-01 00:00:00
abstract:BACKGROUND:Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by beneficial nutrients in fish containing MeHg...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.1104494
更新日期:2012-06-01 00:00:00
abstract::The purpose of the investigation is to study whether an increased mortality from certain causes exists in an area around the Rönnskärsverken smelter works in northern Sweden. Founded in 1928, this metallurgical plant processing mainly nonferrous metals has since its initial operations been using ore with a high arseni...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7719133
更新日期:1977-08-01 00:00:00
abstract::In an attempt to elucidate the relationship between DNA adduct formation and tumorigenesis, DNA adducts were measured in the livers and bladders of mice during chronic exposure to several different doses of 2-acetylaminofluorene (2-AAF) and 4-aminobiphenyl (4-ABP). Continuous oral administration of these compounds for...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.94102s6161
更新日期:1994-10-01 00:00:00
abstract:BACKGROUND:Previous studies have suggested an effect of high arsenic concentration on cognitive and neurobehavioral function in humans. OBJECTIVE:Our goal was to identify demographic and nutritional factors that are associated with As exposure and the influence of this exposure on cognitive function in school-age chil...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9961
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Miners inhaling respirable coal dust (CD) frequently develop coal workers' pneumoconiosis, a dust-associated pneumoconiosis characterized by lung inflammation and variable fibrosis. Many coal miners are also exposed to polycyclic aromatic hydrocarbon (PAH) components of diesel engine exhaust and cigarette sm...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8906
更新日期:2006-09-01 00:00:00
abstract::Inhaled asbestos fibers may contribute to three-fourths of malignant mesotheliomas diagnosed in men and almost 40% of cases diagnosed in women. Bans on the manufacture and sale of amphibole asbestos fibers are expected to reduce the incidence of mesothelioma, but the long latency period from initial exposure to clinic...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0900868
更新日期:2010-03-01 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 APHENA (AIR POLLUTION AND HEALTH: A Combined European and North American Approach) study is a collaborative analysis of multicity time-series data on the effect of air pollution on population health, bringing together data from the European APHEA (Air Pollution and Health: A European Approach) and U.S. N...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.11345
更新日期:2008-11-01 00:00:00
abstract::Exposure to aflatoxin B1 (AFB1), an important cofactor in the etiology of hepatocellular carcinoma in Taiwan, is influenced by dietary and other factors. The present study examined the intraindividual variability in AFB1-albumin adducts, the most reliable long-term biomarker of AFB1 exposure, and whether the baseline ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.01109833
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with alterations in ovarian function and hormones in animals, it has not been studied in humans. On 10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later, we init...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9667
更新日期:2007-03-01 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::The effects of chrysotile on DNA synthesis in the gastrointestinal tract of the rat were studied by measuring the uptake of tritium-labeled thymidine; whole stomach, small intestine, colon liver were removed, cleaned, and homogenized and the DNA was isolated and assayed for tritium label.A dose-response study indicate...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.749319
更新日期:1974-12-01 00:00:00
abstract::A co-culture clonal survival assay was developed to measure the cytotoxicity of test chemical treatments to BALB/c-3T3 cells because the standard clonal survival assay using 200 wild type (WT) cells frequently overestimates chemical cytotoxicity when compared with identical treatment doses in high-density cultures. Th...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.93101s2311
更新日期:1993-07-01 00:00:00
abstract:BACKGROUND:In the developing brain, serotonin (5HT) systems are among the most sensitive to disruption by organophosphates. OBJECTIVES:We exposed neonatal rats to daily doses of diazinon or parathion on postnatal days (PND)1-4 and evaluated 5HT receptors and the 5HT transporter in brainstem and forebrain on PND5, focu...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9337
更新日期:2006-10-01 00:00:00
abstract::We have developed and applied a new measurement methodology to investigate dermal absorption of chloroform while bathing. Ten subjects bathed in chlorinated water while breathing pure air through a face mask. Their exhaled breath was delivered to a glow discharge source/ion trap mass spectrometer for continuous real-t...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.98106337
更新日期:1998-06-01 00:00:00
abstract::The formation of reactive oxygen species resulting from the interaction of silica dust particles with red blood cell membranes was investigated; particularly, the effect of surface hydroxyl (silanol) group concentration on the rate of formation of such reactive oxygen species was investigated. The rate of formation wa...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9087337
更新日期:1990-07-01 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::The disruption of the reproductive system of male and female animals in the wild has been attributed to environmental chemicals (xenobiotics). The effects seen mirror alterations one might anticipate if the steroid hormone-dependent processes that regulate these systems were impaired. To determine whether xenobiotics ...
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
abstract:BACKGROUND:Pregnancy is a sensitive condition during which adverse environmental exposures should be monitored thoroughly and minimized whenever possible. In particular, the hormone balance during gestation is delicate, and disturbance may cause acute or chronic long-term health effects. A potential endocrine disruptio...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP4860
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. OBJECTIVE:We aimed to assess the toxicity of well-characte...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0800121
更新日期:2009-04-01 00:00:00
abstract::Tobacco smoke contains a number of genotoxic compounds that are metabolized to their biologically active forms that subsequently react with cellular DNA to form covalently bound carcinogen-DNA adducts. Several analytical procedures have been developed to detect these adducts in human tissues. Using the nuclease P1-enh...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9399229
更新日期:1993-03-01 00:00:00