Abstract：
:To examine the magnitude of human variability across the entire transcriptome after chemical challenge, we profiled gene expression responses to three different prototypic chemical inducers in primary human hepatocyte cultures from ten independent donors. Correlation between basal expression in any two hepatocyte donors ranged from r(2) values of 0.967 to 0.857, and chemical treatment tended to negatively impact correlation between donors. Including anticipated target genes, 10,812, 8373, and 7847 genes were changed in at least one donor by Aroclor 1254 (A1254), di(2-ethylhexyl) phthalate (DEHP), and phenobarbital (PB), respectively. A subset of these gene targets (n=41) were altered with a high level of reproducibility in at least 9 donors, gene responses that correlated well with literature-reported mechanism of action. Filtering responses to the level of gene subsets clarified the biological impact associated with the respective chemical effectors, in lieu of substantial interindividual variation among donor responses. In these respects, the use of hierarchical clustering methods successfully grouped seven of the ten donors into chemical-specific rather than donor-specific clusters. However, at the whole-genome level, the magnitude of conserved gene expression changes among donors was surprisingly small, with fewer than 50% of the gene responses altered by a single chemical conserved in more than one donor. The use of higher level descriptors, such as those defined by the PANTHER classification system, may enable more consistent categorization of gene expression changes across individuals, as increased reproducibility was identified using this method.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Goyak KM,Johnson MC,Strom SC,Omiecinski CJdoi
10.1016/j.taap.2008.04.024subject
Has Abstractpub_date
2008-09-01 00:00:00pages
216-24issue
2eissn
0041-008Xissn
1096-0333pii
S0041-008X(08)00199-3journal_volume
231pub_type
杂志文章abstract：:A BLU:Ha newborn mouse lung adenoma bioassay was employed to compare the tumorigenicity of selected mononitroarenes and unsubstituted parent compounds 6 months after initial treatment. The presence of a nitro group had a variable effect upon compound potency in which tumorigenicity was increased, abolished, or unchang...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90162-2
更新日期：1989-07-01 00:00:00
abstract：:The DDT metabolite 3-methylsulfonyl-DDE (3-MeSO(2)-DDE) has been proposed as a lead compound for an improved adrenocortical carcinoma (ACC) treatment. ACC is a rare malignant disorder with poor prognosis, and the current pharmacological therapy o,p'-DDD (mitotane) has limited efficacy and causes severe adverse effects...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.10.018
更新日期：2010-02-01 00:00:00
abstract：:The disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was investigated in rainbow trout (Oncorhynchus mykiss) in order to better understand the metabolic and physiological factors that modulate the fate of this extremely toxic compound in rainbow trout compared to other species. The fish were dosed ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0183
更新日期：1996-08-01 00:00:00
abstract：:The disappearance rate of renin from plasma was evaluated in both acutely and chronically lead-exposed rabbits. In addition, the effects of lead (Pb) on in vitro renin secretion were determined with rabbit renal cortical slices. Rabbits acutely exposed to Pb (0.3 to 2.0 mg/kg, iv) demonstrated no increase in plasma re...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90127-8
更新日期：1983-06-15 00:00:00
abstract：:Toxic cardiovascular effects of allylamine and beta-aminopropionitrile were studied in adult male Sprague-Dawley rats given allylamine alone (AA), 100 mg/kg/day, beta-aminopropionitrile alone (beta APN), 1 g/kg/day, or both chemicals (AA + beta APN) by gavage. Rats were given a total of 10 doses in 11 days. Rats given...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90231-i
更新日期：1990-04-01 00:00:00
abstract：:Methylene chloride (dichloromethane, DCM) is metabolized by two pathways: one dependent on oxidation by mixed function oxidases (MFO) and the other dependent on glutathione S-transferases (GST). A physiologically based pharmacokinetic (PB-PK) model based on knowledge of these pathways was used to describe the metaboli...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90281-x
更新日期：1987-02-01 00:00:00
abstract：:The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungst...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2010.04.021
更新日期：2011-07-15 00:00:00
abstract：:WHO has highlighted the need to evaluate dermal toxicity of mycotoxins including Patulin (PAT), detected in several fruits. In this study the skin carcinogenic potential of topically applied PAT was investigated. Single topical application of PAT (400 nmol) showed enhanced cell proliferation (~2 fold), along with incr...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.09.012
更新日期：2011-12-01 00:00:00
abstract：:Trichloroacetate (TCA) and dichloroacetate (DCA) have been shown to be hepatocarcinogenic in mice when administered in drinking water. However, DCA produces pathological effects in the liver that are much more severe than those observed following TCA treatment in both rats and mice. To identify potential mechanisms in...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(92)90332-m
更新日期：1992-08-01 00:00:00
abstract：:Ochratoxin A (OTA) is a mycotoxin that is found in various food and feed products. The molecular mechanisms that are associated with OTA hepatotoxicity and teratogenicity have not been extensively elucidated in a developing organism. In this study, the transcriptomic profile of zebrafish embryos indicates that hemosta...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2017.12.012
更新日期：2018-02-01 00:00:00
abstract：:Isolated rat lymphocytes in salts-glucose medium (pH 7.2) were incubated with nickel chloride, nickel acetate, nickel sulfate, and a soluble form of nickel subsulfide (0-2 mM) at 37 degrees C for 2 h. The soluble form of nickel subsulfide induced a significant increase in DNA-protein crosslinks (DPXLs) (111%) beginnin...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.9097
更新日期：2001-02-01 00:00:00
abstract：:Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation a...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2017.03.022
更新日期：2017-06-01 00:00:00
abstract：:Clofibric acid (CA), a potent peroxisome proliferator (PP), has been shown to cause tumor formation in rat liver. The precise mechanism of action of PPs remains largely unknown. However, it has been proposed that they act by increasing reactive oxygen species (ROS), leading to a cellular oxidative stress. In the prese...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2001.9214
更新日期：2001-08-01 00:00:00
abstract：:The elevation of intracellular Ca2+ in various tissue through oxidative stress induced by menadione has been well documented. Increase of Ca2+ level in platelets results in aggregation of platelets. To test the hypothesis that menadione-induced Ca2+ elevations can play a role in platelet aggregation, we have studied t...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0092
更新日期：1996-05-01 00:00:00
abstract：:Mast cells reside at interfaces with the environment, including the mucosa of the respiratory and gastrointestinal tracts. This localization exposes mast cells to inhaled, or ingested, environmental challenges. In the airways of smokers, resident immune cells will be in contact with the condensed components of cigaret...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2004.09.003
更新日期：2005-04-15 00:00:00
abstract：:Chlorhexidine (CHX), widely used as antiseptic and therapeutic agent in medicine and dentistry, has a toxic effect both in vivo and in vitro. The intrinsic mechanism underlying CHX-induced cytotoxicity in eukaryotic cells is, however, still unknown. A recent study from our laboratory has suggested that CHX may induce ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.10.012
更新日期：2009-01-15 00:00:00
abstract：:The objective of this study was to evaluate an alternative mucosal irritation test using the slug Arion lusitanicus as test organism. The effect of 28 reference substances on the mucosal tissue of the slugs was determined by the amount of mucus produced, the reduction in body weight, and the release of proteins from t...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2002.9444
更新日期：2002-07-15 00:00:00
abstract：:Application of global gene expression analysis in the study of mechanisms of toxicity could provide a more comprehensive interpretation of the molecular basis of drug action. WAY-144122 has pharmacological activity against several targets improving insulin responsiveness and favorably altering lipid profiles. Normal r...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2003.11.016
更新日期：2004-04-01 00:00:00
abstract：:H-ras oncogenes have been identified in greater than 50% of the most common forms of human neoplasia. Ras-related proteins have been postulated to mediated signal transduction pathways involving mitogen-activated protein (MAP) kinases and nuclear responses that may be involved in the induction of apoptosis. We examine...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0264
更新日期：1996-11-01 00:00:00
abstract：:Growing use of carbon nanotubes (CNTs) have garnered concerns regarding their association with adverse health effects. Few studies have probed how CNTs affect a host's susceptibility to pathogens, particularly respiratory viruses. We reported that exposure of lung cells and mice to pristine single-walled CNTs (SWCNTs)...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2020.115167
更新日期：2020-10-01 00:00:00
abstract：:The synergistic percutaneous enhancement between insect repellent DEET and sunscreen oxybenzone has been proven in our laboratory using a series of in vitro diffusion studies. In this study, we carried out an in vivo study to characterize skin permeation profiles from topical skin application of three commercially ava...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.05.016
更新日期：2007-09-01 00:00:00
abstract：:Defects in tryptophan metabolism on the l-kynurenine pathway (KP) are implicated in a number of human diseases, including chronic kidney disease, brain edema or injury, tuberculosis and malaria - as well as cancer, neurodegenerative and autoimmune disorders. However, it is unclear to what extent detrimental effects of...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.01.004
更新日期：2018-02-15 00:00:00
abstract：:Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic le...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.11.012
更新日期：2006-07-01 00:00:00
abstract：:Carcinogenic chromium (VI) compounds are persistent environmental contaminants with potential for human exposure through drinking water. One lesion associated with chromium (VI) exposure is the formation of DNA-protein crosslinks (DPC). In an attempt to develop markers of chromium exposure, the formation of DPC in lym...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(91)90191-g
更新日期：1991-06-01 00:00:00
abstract：:Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2004.04.010
更新日期：2004-11-01 00:00:00
abstract：:2,2,4-Trimethylpentane (TMP), a component of unleaded gasoline, causes nephrotoxicity in male, but not in female, rats. In the present study, male and female Fischer 344 rats were treated with a single oral dose of [14C]TMP (4.4 mmol/kg; 2 microCi/mmol). Radiolabeled material in kidney, liver, and plasma was determine...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90098-6
更新日期：1987-11-01 00:00:00
abstract：:Two lines of evidence support the concept that cardiotoxin from Naja naja siamensis interacts directly with the plasma membrane to produce selective cytolysis of lymphocytes. Toxin adsorbed to the wells of microtiter plates retained the ability to lyse murine T-lymphocytes, but lost the ability to destroy natural kill...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90303-c
更新日期：1990-06-15 00:00:00
abstract：:The disposition of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), a highly toxic environmental contaminant which accumulates in human tissues, was examined in the male Fischer rat after iv and oral exposure. Greater than 70% of an oral dose of 0.1, 0.5, or 1.0 mumol PeCDF/kg body wt was absorbed by the gastrointestinal sy...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90332-2
更新日期：1987-09-15 00:00:00
abstract：:Air pollution particles (PM) are known to elicit an acute inflammatory response in vivo that is mediated in part through PM-induced activation of the NF-kappaB signaling pathway. Many of the details of this process and particularly where in the cell it occurs are unclear. To determine whether contact of PM particles w...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.01.013
更新日期：2005-10-01 00:00:00
abstract：:Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using 1H NMR...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.03.003
更新日期：2012-05-01 00:00:00
