Abstract:
:The accumulation of genetic damage in the forms of activated proto-oncogenes and inactivated tumor-suppressor genes is the driving force in the evolution of a normal cell to a malignant cell. For example, both the activation of ras oncogenes and the inactivation of several suppressor genes, including p53, have been observed in the development of human colon and lung tumors. Point mutations in key codons can activate ras proto-oncogenes and inactivate the p53 suppressor gene. Thus, several critical genes for tumorigenesis are potential targets for carcinogens and radiation that can induce point mutations at low doses. The ras proto-oncogenes are targets for many genotoxic carcinogens. Activation of the ras gene is an early event--probably the "initiating" step--in the development of many chemical-induced rodent tumors. ras Oncogenes are observed in more human tumors and at a higher frequency than any other oncogene, and activation of the proto-oncogene may occur at various stages of the carcinogenic process. Numerous proto-oncogenes other than the ras genes have been shown to be activated in human tumors and to a lesser extent in rodent tumors. Mechanisms that induce aberrant expression of proto-oncogenes are gene amplification and chromosomal translocation or gene rearrangement. Amplification of proto-oncogenes and possibly gene overexpression during the absence of gene amplification occur in the development of many human tumors. For a specific tumor type, amplification of any one proto-oncogene may occur at a low frequency, but the frequency of tumors in which at least one proto-oncogene is amplified can be much higher. Proto-oncogene amplification is usually associated with late stages of tumor progression; however, amplified HER2/neu has been observed in early clinical stages of mammary neoplasia. Activation of proto-oncogenes by chromosomal translocation has been detected at a high frequency in several hematopoietic tumors. Non-ras genes have been detected by DNA transfection assays in both human and rodent tumors. For example, ret and trk genes were found to be activated by gene rearrangements in human papillary thyroid carcinomas. Several potentially new types of oncogenes have also been detected by DNA transfection assays. The etiology of the genetic alterations observed in most human tumors is unclear at present. Examples of ras gene activation and those documented for mutations in the p53 gene demonstrate that exogenous conditions can induce oncogenic mutants of normal genes. The genetic alterations observed in most human tumors are probably generated by both spontaneous events and exogenous conditions.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Anderson MW,Reynolds SH,You M,Maronpot RMdoi
10.1289/ehp.929813subject
Has Abstractpub_date
1992-11-01 00:00:00pages
13-24eissn
0091-6765issn
1552-9924journal_volume
98pub_type
杂志文章,评审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:Studies estimating health effects of long-term air pollution exposure often use a two-stage approach: building exposure models to assign individual-level exposures, which are then used in regression analyses. This requires accurate exposure modeling and careful treatment of exposure measurement error. OBJEC...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1206010
更新日期:2013-09-01 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:BACKGROUND:Developmental exposure to polychlorinated biphenyls (PCBs) or methylmercury (MeHg) can result in a variety of neurotoxic effects, including long-term auditory deficits. However, little is known about the effects of combined exposure to PCBs and MeHg on auditory function. OBJECTIVE:We developmentally exposed...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0800428
更新日期:2009-07-01 00:00:00
abstract::Determination of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in fly ash and cinders collected from nine municipal incinerators in Japan was made. The concentrations of PCDDs and PCDFs in this study were generally in the same range as those in Europe and North America. However, t...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.59-1568091
更新日期:1985-02-01 00:00:00
abstract::Although allergic diseases such as asthma and hay fever are a major cause of morbidity in industrialized countries, most studies have focused on patterns of prevalence among children and adolescents, with relatively few studies on variations in prevalence by race/ethnicity and socioeconomic position among adults. Our ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.02110s2211
更新日期:2002-04-01 00:00:00
abstract::This paper summarizes the clinical phenomenology of multiple chemical sensitivity (MCS), outlines the concepts and evidence for the olfactory-limbic, neural sensitization model for MCS, and discusses experimental design implications of the model for exposure-related research. Neural sensitization is the progressive am...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.97105s2457
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Lead (Pb) exposure has been associated with a host of pathological conditions in humans. In rodents Pb exposure has been shown to alter the hypothalamic-pituitary-adrenal (HPA) axis function. OBJECTIVE:We investigated the effects of lead on responses of the HPA axis to a psychosocial laboratory stressor adm...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1103873
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.0900591
更新日期:2009-11-01 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::Lead is a male reproductive toxicant. Data suggest that rats dosed with relatively high levels of lead acetate for short periods of time induced changes in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level, but these changes were attenuated with increased concentration of exposure. The curr...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.02110871
更新日期:2002-09-01 00:00:00
abstract::In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, l...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.8774153
更新日期:1987-10-01 00:00:00
abstract::Pyrethroids are important insecticides used in agriculture, forestry, horticulture, and in the home. In humans, they are rapidly metabolized and renally eliminated. In numerous studies, pyrethroid metabolites have been detected in urine after occupational exposure to insecticides. In this study, we used a new, reliabl...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.01109213
更新日期:2001-03-01 00:00:00
abstract::To elucidate the effect of intake of mutagenic and/or carcinogenic pyrolysis products of proteins and amino acids on carcinogenesis in man, we have undertaken two epidemiologic cohort studies: one concerning the possible association of broiled fish consumption with cancer and the other concerning the cancer mortality ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8667143
更新日期:1986-08-01 00:00:00
abstract:BACKGROUND:Psychological sequelae are among the most pronounced effects in populations following exposure to oil spills. Women in particular represent a vulnerable yet influential population but have remained relatively understudied with respect to the Deepwater Horizon oil spill (DHOS). OBJECTIVE:To describe the rela...
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:BACKGROUND:Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine-disrupting compounds (EDCs) share a high degree of structural si...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1002635
更新日期:2011-04-01 00:00:00
abstract::Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmen...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.8195
更新日期:2005-11-01 00:00:00
abstract::Millions of people worldwide are exposed to arsenic-contaminated drinking water, and ingestion of inorganic arsenic (InAs) has been associated with increased risks of cancer. The primary metabolic pathway of ingested InAs is methylation to monomethyl arsenic (MMA) and dimethyl arsenic (DMA). However, people vary great...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.7907
更新日期:2005-09-01 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:BACKGROUND:Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity. METHODS:The nematode Caenorhabditis elegan...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1409645
更新日期:2016-05-01 00:00:00
abstract::Implementation of the Toxic Substances Control Act of 1977 creates the need to reliably establish testing priorities because laboratory resources are limited and the number of industrial chemicals requiring evaluation is overwhelming. The use of quantitative structure activity relationship (QSAR) models as rapid and p...
journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
doi:10.1289/ehp.8771171
更新日期:1987-04-01 00:00:00
abstract::Children may be more susceptible to exposures to environmental toxins than adults and may be more vulnerable to their effects. Because of this, the health care community and those responsible for children need to be alert to possible environmental factors in identifying and responding to the health problems of childre...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.95103s613
更新日期:1995-09-01 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::The workshop "Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels" was held to provide a forum for discussions and recommendations of methods and data needed to improve risk assessments of endocrine disruptors. This article was produced by a working group charged with de...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.99107s4605
更新日期:1999-08-01 00:00:00
abstract::The lysosomes of several varieties of cells such as the tubular proximal cell of the kidney and the alveolar macrophage have the ability to concentrate and precipitate several elements inhaled in water-soluble form, usually as phosphate. The mechanism involved is attributed to the high acid phosphatase activity of lys...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.9297145
更新日期:1992-07-01 00:00:00
abstract:BACKGROUND:The effect of indoor nitrogen dioxide concentrations on asthma morbidity among inner-city preschool children is uncertain. OBJECTIVES:Our goal was to estimate the effect of indoor NO2 concentrations on asthma morbidity in an inner-city population while adjusting for other indoor pollutants. METHODS:We recr...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.11349
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND:Human controlled-exposure studies have assessed the impact of ambient fine particulate matter on cardiac autonomic function measured by heart rate variability (HRV), but whether these effects are modified by concomitant ozone exposure remains unknown. OBJECTIVE:In this study we assessed the impact of O(3) a...
journal_title:Environmental health perspectives
pub_type: 杂志文章,随机对照试验
doi:10.1289/ehp.0900541
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants and are becoming a ubiquitous environmental contaminant. Adverse effects in the developing brain are of great health concern. OBJECTIVE:We investigated the effect of PBDEs/hydroxylated PBDEs (OH-PBDEs) on thyroid hormone (TH) receptor...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/ehp.1002065
更新日期:2011-02-01 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:BACKGROUND:Evidence indicates that air pollution contributes to cardiopulmonary mortality. There is ongoing debate regarding the size and shape of the pollution–mortality exposure–response relationship. There are also growing appeals for estimates of pollution–mortality relationships that use public data and are based ...
journal_title:Environmental health perspectives
pub_type: 杂志文章
doi:10.1289/EHP4438
更新日期:2019-07-01 00:00:00