Abstract:
:Exposure of human bladder urothelial cells (UROtsa) to 50 nM of the arsenic metabolite, monomethylarsonous acid (MMA(III)), for 12 weeks results in irreversible malignant transformation. The ability of continuous, low-level MMA(III) exposure to cause an increase in genotoxic potential by inhibiting repair processes necessary to maintain genomic stability is unknown. Following genomic insult within cellular systems poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger protein, is rapidly activated and recruited to sites of DNA strand breaks. When UROtsa cells are continuously exposed to 50 nM MMA(III), PARP-1 activity does not increase despite the increase in MMA(III)-induced DNA single-strand breaks through 12 weeks of exposure. When UROtsa cells are removed from continuous MMA(III) exposure (2 weeks), PARP-1 activity increases coinciding with a subsequent decrease in DNA damage levels. Paradoxically, PARP-1 mRNA expression and protein levels are elevated in the presence of continuous MMA(III) indicating a possible mechanism to compensate for the inhibition of PARP-1 activity in the presence of MMA(III). The zinc finger domains of PARP-1 contain vicinal sulfhydryl groups which may act as a potential site for MMA(III) to bind, displace zinc ion, and render PARP-1 inactive. Mass spectrometry analysis demonstrates the ability of MMA(III) to bind a synthetic peptide representing the zinc-finger domain of PARP-1, and displace zinc from the peptide in a dose-dependent manner. In the presence of continuous MMA(III) exposure, continuous 4-week zinc supplementation restored PARP-1 activity levels and reduced the genotoxicity associated with MMA(III). Zinc supplementation did not produce an overall increase in PARP-1 protein levels, decrease the levels of MMA(III)-induced reactive oxygen species, or alter Cu-Zn superoxide dismutase levels. Overall, these results present two potential interdependent mechanisms in which MMA(III) may increase the susceptibility of UROtsa cells to genotoxic insult and/or malignant transformation: elevated levels of MMA(III)-induced DNA damage through the production of reactive oxygen species, and the direct MMA(III)-induced inhibition of PARP-1.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Wnek SM,Kuhlman CL,Camarillo JM,Medeiros MK,Liu KJ,Lau SS,Gandolfi AJdoi
10.1016/j.taap.2011.08.029subject
Has Abstractpub_date
2011-11-15 00:00:00pages
1-13issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(11)00343-7journal_volume
257pub_type
杂志文章abstract::Male Wistar rats pretreated with ethanol (2.0 g in 80 ml liquid diet/day for 3 weeks) or phenobarbital (PB, 80 mg/kg/day ip for 4 days) were exposed by inhalation to 500, 1000, 2000, 4000, or 8000 ppm trichloroethylene (TRI) for 2 or 8 hr, and the blood concentration of TRI and the urinary concentration of TRI metabol...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90264-5
更新日期:1988-06-30 00:00:00
abstract::Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsoni...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.05.005
更新日期:2006-10-01 00:00:00
abstract::Tetrandrine, an herbal drug, has been employed in China to treat pulmonary fibrosis. To date, the mechanisms governing the antifibrotic action of tetrandrine are unknown. The present study employs a fibroblast mitogenic assay to determine whether tetrandrine directly inhibits the ability of fibroblasts to respond to s...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1173
更新日期:1993-09-01 00:00:00
abstract::The commonly used antidepressants imipramine, amitriptyline, and nortriptyline were found to significantly inhibit human natural killer (NK) cell-mediated cytolysis in vitro and suppress the stimulation of NK cells by IFN-gamma. This is a previously unrecognized biologic property of these drugs with psychotropic activ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0068
更新日期:1996-04-01 00:00:00
abstract::Inhalation of methyl chloride (CH3Cl) by male B6C3F1 mice resulted in a concentration-dependent depletion of glutathione (GSH) in liver, kidney, and brain. Exposure for 6 hr to 100 ppm CH3Cl decreased the concentration of GSH in mouse liver by 45%, while exposure to 2500 ppm for 6 hr lowered liver GSH to approximately...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90115-7
更新日期:1984-03-15 00:00:00
abstract::Cadmium is a widespread environmental contaminant present in food. The absorption in the intestine increases in individuals with low iron stores, but the effect of zinc deficiency is not clear. The aim of the present study was to assess the influence of iron and zinc status on cadmium accumulation in pregnant Banglade...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.04.009
更新日期:2007-07-15 00:00:00
abstract::Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.08.015
更新日期:2015-11-01 00:00:00
abstract::Diabetes is known to potentiate thioacetamide (TA)-induced liver injury via enhanced bioactivation. Little attention has been given to the role of compensatory tissue repair on ultimate outcome of hepatic injury in diabetes. The objective of this study was to investigate the effect of diabetes on TA-induced liver inju...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2000.8952
更新日期:2000-07-15 00:00:00
abstract::Deltamethrin, a widely used type II pyrethroid insecticide, is a relatively potent neurotoxicant. While the toxicity has been extensively examined, toxicokinetic studies of deltamethrin and most other pyrethroids are very limited. The aims of this study were to identify, characterize, and assess the relative contribut...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.07.021
更新日期:2006-04-15 00:00:00
abstract::Trimethyltin (TMT), is a hippocampal neurotoxicant characterized by neuronal degeneration, astrogliosis, and microglia reactivity with an associated elevation in proinflammatory cytokine mRNA levels. To examine the role of proinflammatory cytokines in the TMT-induced glia response, mixed cortical glia cultures were ex...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2002.9390
更新日期:2002-05-01 00:00:00
abstract::An experimental system was chosen to investigate the bioactivity of a lipoprotein-sequestered toxicant at the cellular level based on recent studies demonstrating receptor-mediated uptake of lipoproteins by macrophages. Rat peritoneal exudate cell suspensions (PEC) were exposed to DDT and lipoprotein-sequestered DDT, ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90282-6
更新日期:1986-03-15 00:00:00
abstract::Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validat...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.04.028
更新日期:2012-08-01 00:00:00
abstract::Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.07.012
更新日期:2014-10-01 00:00:00
abstract::Metallothioneins (MTs) are ubiquitous low-molecular-weight proteins that are induced by a variety of inducers, including metals, lipopolysaccharides (LPS), cytokines, oxidative stress, etc., and are thought to play a protective role against various toxic insults. The constitutive level of metallothionein is an importa...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1056
更新日期:1995-03-01 00:00:00
abstract::Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered t...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.08.014
更新日期:2008-12-01 00:00:00
abstract::It has been suggested that airway irritation, by acting as an adjuvant, as well as producing damage, may be an important factor related to asthma. The present study examined the window of time following acute upper and lower airway irritant exposure to determine the period of increased risk of immunological sensitizat...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8148
更新日期:1997-06-01 00:00:00
abstract::It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared α7 and β2 nAChR subunit expression in eight nuclei of the caudal and ro...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.09.023
更新日期:2011-12-15 00:00:00
abstract::The pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) were measured in the beagle dog and rhesus monkey and compared with the kinetics observed in rats and humans. In addition, studies were conducted in anesthetized dogs to better understand the mechanism by which [14C]triclopyr is eliminated i...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8136
更新日期:1997-06-01 00:00:00
abstract::The mechanism of liver cell injury induced by an overdose of the analgesic acetaminophen (AAP) remains controversial. Recently, it was hypothesized that a significant number of hepatocytes die by apoptosis. Since caspases have been implicated as critical signal and effector proteases in apoptosis, we investigated thei...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8635
更新日期:1999-05-01 00:00:00
abstract::The industrial solvent ethylene glycol monomethyl ether (EGME) is a known teratogen that has been reported to alter calcium metabolism in guinea pigs during chronic exposure. Because of the tremendous demand of reproduction on maternal calcium stores, the effects of EGME on calcium and vitamin D metabolism during gest...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90050-5
更新日期:1986-11-01 00:00:00
abstract::Ah receptor was identified and characterized in cytosol and nuclear extracts from the rainbow trout hepatoma cell line RTH-149. The cytosolic receptor was detectable with both halogenated ([3H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) and non-halogenated ([3H]3-methylcholanthrene and [3H]benzo[a]pyrene) aromatic hyd...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90105-4
更新日期:1990-10-01 00:00:00
abstract::Low dietary concentrations of methionine and cysteine are known to decrease hepatic glutathione content. However, it is not known if restricting the dietary content of these sulfur containing amino acids also affects hepatic levels of adenosine 3'-phosphate 5'-phosphosulfate (PAPS), the cofactor for sulfation, or meta...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90025-p
更新日期:1990-02-01 00:00:00
abstract::Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. Arsenic effects on platelets, which are important in development of cardiovascular disease, were examined in vitro and in a drinking water study using a rat animal model. Trivalen...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9356
更新日期:2002-03-01 00:00:00
abstract::In many neuropathologies activated microglia and macrophages cause neurotoxicity and prolong the inflammatory response. We have previously characterized the glycosphingolipid Neurostatin (Nst), which potentially reduces these detrimental mechanisms. Nst, isolated from mammalian brain, is the GD1b ganglioside with O-ac...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114627
更新日期:2019-08-15 00:00:00
abstract::Hexachlorobenzene (HCB)-induced porphyria occurs in female, but not male, rats after a delay of 35 days following HCB treatment. Uroporphyrinogen decarboxylase (UROD) inhibition has been proposed as a primary causative event. To determine whether there also exists a delay phase and a sexual dimorphism for UROD inhibit...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8157
更新日期:1997-07-01 00:00:00
abstract::Tolerance to several toxic effects of Cd, including lethality, has been shown following pretreatment with Cd. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity. Rats were challenged with Cd (2.0, 3.0, 4.0, or 5.0 mg/kg, iv) 24 hr after pretreatment with saline (2 ml/kg, sc) o...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90283-7
更新日期:1984-07-01 00:00:00
abstract::The effects of erythropoiesis on cadmium-metallothionein (Cd-MT)2 levels in spleen, a major erythropoietic tissue, was examined following sc injection of 109CdCl2 into mice. As the concentration of Cd in plasma decreased following injection of 109CdCl2 into control mice, the levels in spleen and liver increased rapidl...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1189
更新日期:1995-10-01 00:00:00
abstract::Exposure of mice to cationic rhodamines, Rh 123 and Rh 6G, has been found to be associated with developmental toxicity, while neutral rhodamines (e.g., Rh B) had no such effect. When mouse embryos from dams given ip injections of Rh 123, Rh 6G (15 mg/kg), or Rh B (30 mg/kg) on gestation Day (GD) 10 were examined, Rh 1...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90113-0
更新日期:1989-06-01 00:00:00
abstract::Fumonisins are carcinogenic to rats and are suspected human carcinogens. However, the mechanism(s) of carcinogenesis of fumonisn B1 (FB1) is poorly understood. Multiple signal transduction pathways such as protein kinase C (PKC) have been shown to play an important role in carcinogenesis. This study was undertaken to ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0274
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND:The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2021.115425
更新日期:2021-01-28 00:00:00