Abstract:
:The X-ray crystallographic structural determinations of synthetic estrogens and antiestrogens provide reliable information on the global minimum energy conformation of these molecules or a local minimum energy conformation that is within 1 or 2 kcal/mole of the global minimum. In favorable cases, state-of-the-art molecular mechanics calculations provide quantitative agreement with X-ray results and information on the relative energy of other local minimum energy conformations not observed crystallographically. Because the conformation of diethylstilbestrol (DES) observed in solvated crystals has an overall conformation and dipole moment more similar to estradiol it is the form more likely to bind to the receptor and produce hormone activity. Either phenol ring of DES can successfully mimic the estradiol A-ring in binding to the receptor. Indenestrol A (INDA) and indenestrol B (INDB) have nearly identical fully extended planar conformations. Either the alpha or gamma rings of these compounds may mimic the A ring of estradiol and compete for the estrogen receptor. Although there are eight distinct ways in which molecules of a racemic mixture of INDA or INDB can bind to the receptor, not all of them may be able to elicit a hormonal response. This may account for the reduced biological activity of the compounds despite their successful competition for receptor binding. The minimum energy conformations of Z-pseudodiethylstilbestrol (ZPD) and E-pseudodiethylstilbestrol (EPD) are bent in a fashion similar to that of indanestrol (INDC). These molecules have good binding affinity suggesting that the receptor does not require a flat molecule. Therefore these conformations would appear to be compatible with receptor binding, but only the Z isomer has an energetically allowed extended conformation that accounts for its observed biological activity relative to DES.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Duax WL,Griffin JF,Weeks CM,Korach KSdoi
10.1289/ehp.8561111subject
Has Abstractpub_date
1985-09-01 00:00:00pages
111-21eissn
0091-6765issn
1552-9924journal_volume
61pub_type
杂志文章,评审abstract::Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent an...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7519
更新日期:2005-03-01 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:BACKGROUND:Air pollution data in Bangkok, Thailand, indicate that levels of particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) are significantly higher than in most cities in North America and Western Europe, where the health effects of PM(10) are well documented. However, the pollution mix, seasona...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.10849
更新日期:2008-09-01 00:00:00
abstract::We present a model of the distribution of noise annoyance with the mean varying as a function of the noise exposure. Day-night level (DNL) and day-evening-night level (DENL) were used as noise descriptors. Because the entire annoyance distribution has been modeled, any annoyance measure that summarizes this distributi...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.01109409
更新日期:2001-04-01 00:00:00
abstract::The possible risk for human health arising from consumption of lead-polluted shellfish was suggested by experiments on the bioavailability for mice of a "biologically detoxified" form of the metal. In this work, young mice were fed with a mixed diet including mussels collected in a Pb-polluted area. Metal concentratio...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s3335
更新日期:1994-09-01 00:00:00
abstract::The effects of global change on biodiversity and ecosystem functioning encompass multiple complex dynamic processes. Climate change and exposure to endocrine-disrupting chemicals (EDCs) are currently regarded as two of the most serious anthropogenic threats to biodiversity and ecosystems. We should, therefore, be espe...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.8057
更新日期:2006-04-01 00:00:00
abstract::We include in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health. These parent CW agents include several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an ...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.99107933
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND:"Airwave" is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a conseq...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0901416
更新日期:2010-06-01 00:00:00
abstract::Haloalkane toxicity originates from attack on biological targets by reactive intermediates derived from haloalkane metabolism by a hemoprotein, cytochrome P-450. Carbon-centered radicals and their peroxyl derivatives are most likely involved. The reactions of iron porphyrin--a model for cytochrome P-450--with various ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.856453
更新日期:1985-12-01 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: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:National disparities in asbestos use will likely lead to an unequal burden of asbestos diseases. OBJECTIVES:As economic status may be linked to asbestos use, we assessed, globally, the relationship between indicators of national economic development and asbestos use. METHODS:For the 135 countries that have...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0901196
更新日期:2010-01-01 00:00:00
abstract::In 1998 we published the results of a study suggesting an association between breast cancer and perchloroethylene (PCE; also called tetrachloroethylene) exposure from public drinking water. The present case-control study was undertaken to evaluate this association further. The cases were composed of female residents o...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.4980
更新日期:2003-02-01 00:00:00
abstract::Asthma is the most common chronic illness of childhood and its prevalence is increasing, causing much concern for identification of risk factors such as air pollution. We previously conducted a study showing a relationship between asthma visits in all persons < 65 years of age to emergency departments (EDs) and air po...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.99107489
更新日期:1999-06-01 00:00:00
abstract::An important public health challenge has been the need to protect children's health. To accomplish this goal, the scientific community needs scientifically based child-specific risk assessment methods. Critical to their development is the need to understand mechanisms underlying children's sensitivity to environmental...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.00108s113
更新日期:2000-03-01 00:00:00
abstract::Concentrations of polychlorinated biphenyls (PCBs), hydroxylated metabolites of PCBs (HO-PCBs) and octachlorostyrene (4-HO-HpCS), and pentachlorophenol (PCP) were determined in umbilical cord plasma samples from three different regions of Québec. The regions studied included two coastal areas where exposure to PCBs is...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.02110411
更新日期:2002-04-01 00:00:00
abstract::Data from experiments on the induction of specific-locus mutations in model systems are used in genetic risk assessment to estimate potential adverse effects in the human population. In such assessments with radiation or chemical mutagens, the following information is required: a) spontaneous and induced forward-mutat...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.94102s183
更新日期:1994-01-01 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:BACKGROUND:The Love Canal is a rectangular 16-acre, 10-ft deep chemical waste landfill situated in a residential neighborhood in Niagara Falls, New York. This seriously contaminated site first came to public attention in 1978. No studies have examined mortality in the former residents of the Love Canal neighborhood (LC...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.11350
更新日期:2009-02-01 00:00:00
abstract::The phenomenon of fiber-induced cytotoxicity to P388D1 macrophagelike cells has been demonstrated to parallel (thus far without exception) the probability that the fiber will induce a pleural sarcoma (mesothelioma) in rats. This startling parallel in both cases seems to be essentially independent of the chemical natur...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.803491
更新日期:1980-02-01 00:00:00
abstract::Man-made endocrine-disrupting chemicals (EDCs) present a threat to biodiversity, even in remote areas. To date, numerous wildlife species have been affected by EDCs in the environment, but it is likely that many more species are suffering effects that have not yet been reported. Impaired reproduction, damaged brain fu...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.8070
更新日期:2006-04-01 00:00:00
abstract::In this study, we evaluated the impact of long-term occupational exposure to elemental mercury vapor (Hg0) on the personality traits of ex-mercury miners. Study groups included 53 ex-miners previously exposed to Hg0 and 53 age-matched controls. Miners and controls completed the self-reporting Eysenck Personality Quest...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7863
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1409360
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND:Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure. OBJEC...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1307736
更新日期:2016-01-01 00:00:00
abstract::Occupational and environmental asbestos exposure continues to represent a public health problem, despite increasingly restrictive laws adopted by most industrialized countries. Peritoneal mesothelioma is a rare and aggressive asbestos-related malignancy. We present the case of a 65-year-old man who developed recurrent...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.6542
更新日期:2004-04-01 00:00:00
abstract:BACKGROUND:Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region. OBJECTIVES:We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.11661
更新日期:2008-11-01 00:00:00
abstract::The pneumoconioses are associated with chronic inflammatory processes during which increased amounts of reactive oxygen species are formed in the lower respiratory tract. To characterize the effect(s) of these processes on the defense system against free radicals, we studied 91 individuals with long-term occupational ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9084165
更新日期:1990-03-01 00:00:00
abstract::In this study we investigated the risk of hearing loss among workers exposed to both toluene and noise. We recruited 58 workers at an adhesive materials manufacturing plant who were exposured to both toluene and noise [78.6-87.1 A-weighted decibels; dB(A)], 58 workers exposed to noise only [83.5-90.1 dB(A)], and 58 ad...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8959
更新日期:2006-08-01 00:00:00
abstract::According to current data, the capacity to cause nonprogrammed or unscheduled cell proliferation in target tissues, a common characteristic of chemical carcinogens, may play a more important role in the development of tumors than does genotoxicity. This paper provides strong support for the validity of this conclusion...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.9610440
更新日期:1996-01-01 00:00:00
abstract::The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) has highly pleiotropic effects on cells in culture and on tissues in vivo, including effects on protein kinase C (PKC) activation and gene expression. In order to determine the mechanism of activation of gene transcription by TPA, DNA sequences whose transc...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.877689
更新日期:1987-12-01 00:00:00