Abstract：
:Male rats were treated with various model compounds or the appropriate vehicle controls. Most substances were either well-known hepatotoxicants or showed hepatotoxicity during preclinical testing. The aim of the present study was to determine if biological samples from rats treated with various compounds can be classified based on gene expression profiles. In addition to gene expression analysis using microarrays, a complete serum chemistry profile and liver and kidney histopathology were performed. We analyzed hepatic gene expression profiles using a supervised learning method (support vector machines; SVMs) to generate classification rules and combined this with recursive feature elimination to improve classification performance and to identify a compact subset of probe sets with potential use as biomarkers. Two different SVM algorithms were tested, and the models obtained were validated with a compound-based external cross-validation approach. Our predictive models were able to discriminate between hepatotoxic and nonhepatotoxic compounds. Furthermore, they predicted the correct class of hepatotoxicant in most cases. We provide an example showing that a predictive model built on transcript profiles from one rat strain can successfully classify profiles from another rat strain. In addition, we demonstrate that the predictive models identify nonresponders and are able to discriminate between gene changes related to pharmacology and toxicity. This work confirms the hypothesis that compound classification based on gene expression data is feasible.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Steiner G,Suter L,Boess F,Gasser R,de Vera MC,Albertini S,Ruepp Sdoi
10.1289/txg.7036subject
Has Abstractpub_date
2004-08-01 00:00:00pages
1236-48issue
12eissn
0091-6765issn
1552-9924journal_volume
112pub_type
杂志文章abstract：:In this study we investigated the potential impact of climate change in Portugal on heat-related mortality, air pollution-related health effects, and selected vectorborne diseases. The assessment used climate scenarios from two regional climate models for a range of future time periods. The annual heat-related death r...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.8431
更新日期：2006-12-01 00:00:00
abstract：:In this study, we determined the biologic activity of dichloromethane-extracted particulate matter < 10 micro m in aerodynamic diameter (PM10) obtained from filters at three sites in the Paso del Norte airshed, which includes El Paso, Texas, USA; Juarez, Chihuahua, Mexico, and Sunland Park, New Mexico, USA. The extrac...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.6058
更新日期：2003-08-01 00:00:00
abstract：BACKGROUND:The association of DDT (dichlorodiphenyltrichloroethane) with breast cancer is controversial, but animal studies directly linking DDT to risk are lacking. Concerns with DDT reside in its environmental persistence, bioaccumulation in breast adipose tissue, and endocrine-disrupting actions. Whereas most attent...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.1104327
更新日期：2012-08-01 00:00:00
abstract：:During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm; 6 hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition coefficient determinations were conducted on female B6C3F1, mice after 1 day, 1 month, 1 year, and 2 years of exposure. Using physiologically based pharmacokine...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.96104858
更新日期：1996-08-01 00:00:00
abstract：:The formamidines, a relatively new group of acaricide-insecticides, are novel both in their range of biological activities and in their mode of action, which is presently unknown. This paper is a review of the historical development, properties, structures, uses, and chemistry of this group of pesticides, with particu...
journal_title：Environmental health perspectives
pub_type： 杂志文章,评审
doi：10.1289/ehp.761457
更新日期：1976-04-01 00:00:00
abstract：:Hemoglobin adducts of the common metabolite of the tobacco-specific nitrosamine (TSNA) 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and of 4-aminobiphenyl (4-ABP) were quantified in blood samples from smokers and nonsmokers to test their suitability for biomonitoring tobacco smoke exposure. Additionally, TSNA adducts were...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.99-1567014
更新日期：1993-03-01 00:00:00
abstract：:We assessed chlorinated hydrocarbon contamination of mink and river otters on the Columbia and Fraser River systems of northwestern North America, in relation to morphological measures of condition. We obtained carcasses of mink and river otters from commercial trappers during the winters 1994-1995 and 1995-1996. Necr...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.99107141
更新日期：1999-02-01 00:00:00
abstract：:Previously, we found that exposure of neonatal rats to chlorpyrifos (CPF) produced brain cell damage and loss, with resultant abnormalities of synaptic development. We used the same biomarkers to examine prenatal CPF treatment so as to define the critical period of vulnerability. One group of pregnant rats received CP...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.021101097
更新日期：2002-11-01 00:00:00
abstract：:Human milk is a repository for certain classes of long-lived, fat-soluble environmental contaminant chemicals. Some members of this class, such as the chlorinated pesticides and the chlorinated biphenyls, can be expected to be present at chemical waste disposal sites. Analysis of samples of breast milk obtained from w...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.834887
更新日期：1983-02-01 00:00:00
abstract：BACKGROUND:Although many studies have examined the effects of air pollution on mortality, data limitations have resulted in fewer studies of both particulate matter with an aerodynamic diameter of
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.0800108
更新日期：2009-06-01 00:00:00
abstract：:Along the Texas-Mexico border, the prevalence of neural tube defects (NTDs) among Mexican-American women doubled during 1990-1991. The human outbreak began during the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin that often contaminates corn. Because Mexican Americans in Texas consume l...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.8221
更新日期：2006-02-01 00:00:00
abstract：:The presence of mycotoxins in grains is well documented. Workers in grain handling occupations are commonly exposed to grain dust aerosols. Work in our laboratory has shown that T-2 toxin is highly toxic to rat alveolar macrophages in vitro, causing loss of viability, release of radiolabeled chromium, inhibition of ma...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.866645
更新日期：1986-04-01 00:00:00
abstract：BACKGROUND:Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of cancer deaths worldwide, with prevalence 16-32 times higher in developing countries than in developed countries. Aflatoxin, a contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus in maize and nuts, is a...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.0901388
更新日期：2010-06-01 00:00:00
abstract：:It has been estimated that 4 of 1,000 live births and 35% of spontaneous abortions are aneuploid and that an important proportion of embryo and newborn aneuploidy is of paternal origin. Exposure to organophosphorous pesticides (OP) has been associated with sperm hyperploidy/polyploidy. Therefore, we aimed to assess th...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.011091237
更新日期：2001-12-01 00:00:00
abstract：:The presence of low concentrations of perchlorate in some drinking water sources has led to concern regarding potential effects on the thyroid. In a recently published report, the National Academy of Sciences indicated that the perchlorate dose required to cause hypothyroidism in adults would probably be > 0.40 mg/kg-...
journal_title：Environmental health perspectives
pub_type： 临床试验,杂志文章
doi：10.1289/ehp.7814
更新日期：2005-08-01 00:00:00
abstract：:The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban. These chemicals may be used in thousands of personal care and consumer products as well as ...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/EHP1788
更新日期：2017-06-20 00:00:00
abstract：:Asthma and lead poisoning are prevalent among urban children in the United States. Lead exposure may be associated with excessive production of immunoglobulin E, possibly increasing asthma risk and contributing to racial disparities. The objective of this study was to examine racial differences in the association of b...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.7453
更新日期：2005-07-01 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：:We have previously reported that rats are resilient to the hepatotoxic and lethal combination of chlordecone (CD) and carbon tetrachloride (CCl4) during early postnatal development. The overall findings pointed to stimulated cell division and tissue repair mechanisms as the underlying cause of resistance. The objectiv...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.98106597
更新日期：1998-09-01 00:00:00
abstract：:The epidemiological data linking air pollution and lung cancer are derived from statistical associations concerning rates of cancer among urban and rural residents, migrant studies and studies of occupational groups exposed to effluents from fossil fuel combinations. Few, if any of these studies, are adequately adjust...
journal_title：Environmental health perspectives
pub_type： 杂志文章,评审
doi：10.1289/ehp.834733
更新日期：1983-01-01 00:00:00
abstract：BACKGROUND:Cancer may be a stem cell (SC)-based disease involving formation of cancer SCs (CSCs) potentially arising from transformation of normal SCs. Cadmium has been linked to human pancreatic cancer. OBJECTIVE:We studied cadmium exposure of human pancreatic ductal epithelial (HPDE) cells and whether SCs may be tar...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.1205082
更新日期：2012-09-01 00:00:00
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 ob...
journal_title：Environmental health perspectives
pub_type： 杂志文章,评审
doi：10.1289/ehp.929813
更新日期：1992-11-01 00:00:00
abstract：:Polybrominated biphenyls (PBBs) cause a mixed-type (phenobarbital- plus 3-methylcholanthrene-like) induction of liver microsomal drug metabolizing enzymes in rats. However, 2,2',4,4',5,5'-hexabromobiphenyl and 2,2',3,4,4',5,5'-heptabromobiphenyl, which together comprise less than 80% of PBBs (FireMaster), were shown t...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.7823159
更新日期：1978-04-01 00:00:00
abstract：:The destruction of the World Trade Center (WTC) on 11 September 2001 in New York City resulted in the massive release of pulverized dust and combustion products. The dust and smoke settled in the surrounding area, which encompassed a large residential community. We hypothesized that previously normal residents in the ...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.7375
更新日期：2005-04-01 00:00:00
abstract：BACKGROUND:Exceptional aging, defined as reaching age 85 years, shows geographic inequalities that may depend on local environmental conditions. Links between particulate pollution-a well-recognized environmental risk factor-and exceptional aging have not been investigated. OBJECTIVES:We conducted a nationwide analysi...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/EHP197
更新日期：2016-11-01 00:00:00
abstract：BACKGROUND:Cigarette smoke exposure in utero and during early postnatal development increases the incidence of asthma and airway hyperresponsiveness (AHR) later in life, suggesting that a possible critical period of developmental sensitivity exists in the prenatal and early postnatal periods. OBJECTIVE:We investigated...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.0800511
更新日期：2009-09-01 00:00:00
abstract：:Chlordane is a polychlorinated hydrocarbon that causes liver enlargement and induces mixed-function oxidases similar to those induced by phenobarbitone in the mouse. We have assessed the hepatocarcinogenicity (after 2 years) and the time course (over 6 months) of liver and thyroid cell proliferation in C57Bl/10J mice ...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.93101s5219
更新日期：1993-12-01 00:00:00
abstract：:We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal at...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.9910775
更新日期：1999-01-01 00:00:00
abstract：:The presence of blue-green algae (BGA) toxins in surface waters used for drinking water sources and recreation is receiving increasing attention around the world as a public health concern. However, potential risks from exposure to these toxins in contaminated health food products that contain BGA have been largely ig...
journal_title：Environmental health perspectives
pub_type： 杂志文章
doi：10.1289/ehp.00108435
更新日期：2000-05-01 00:00:00
abstract：:The unique nonrespiratory functions of the lungs have become more apparent in recent years. The isolated perfused lung model offers many advantages over other methods for the study of pulmonary metabolism, xenobiotic disposition and the influence of interactions among agents of different physical forms. Detailed descr...
journal_title：Environmental health perspectives
pub_type： 杂志文章,评审
doi：10.1289/ehp.845635
更新日期：1984-06-01 00:00:00
