Abstract:
:Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Mathew ST,Bergström P,Hammarsten Odoi
10.1016/j.taap.2014.02.013subject
Has Abstractpub_date
2014-05-01 00:00:00pages
188-94issue
3eissn
0041-008Xissn
1096-0333pii
S0041-008X(14)00058-1journal_volume
276pub_type
杂志文章abstract:OBJECTIVE:To provide insights into the mode of action for Ni3S2 lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. METHODS:Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer 344 rats following inhalation of Ni3S2 at 0.0,...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.06.007
更新日期:2014-09-15 00:00:00
abstract::Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and pre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.03.009
更新日期:2016-06-01 00:00:00
abstract::Acetaminophen (APAP) administration (600 mg/kg, ip) to 18-hr fasted, 3-month-old male CD-1 mice results in necrosis of the convoluted renal proximal tubules with a corresponding elevation of plasma urea nitrogen (BUN). Administration of the gamma-glutamyl transpeptidase inhibitor, L-(alpha S,5S)-alpha-amino-3-chloro-4...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0020
更新日期:1996-01-01 00:00:00
abstract::Methyl chloride (MeCl) metabolism and pharmacokinetics were studied in male Fischer 344 rats and male beagle dogs. Apparent steady-state blood MeCl concentrations were proportionate to exposure concentration in rats and dogs exposed to 50 and 1000 ppm. Furthermore, blood MeCl concentrations were similar in both specie...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(83)90292-2
更新日期:1983-05-01 00:00:00
abstract::The embryotoxic and teratogenic potential of inhaled monochlorobenzene (MCB) was evaluated in rats and rabbits. Bred Fischer 344 rats and inseminated New Zealand White rabbits were exposed to 0, 75, 210, or 590 ppm of MCB via inhalation for 6 hr/day during the period of major organogenesis. Exposure to 590 ppm caused ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90018-8
更新日期:1984-11-01 00:00:00
abstract::Intravesical gemcitabine has recently been introduced for the treatment of superficial bladder cancer and has a favourable efficacy and toxicity profile in comparison to mitomycin c (MMC), the most commonly used chemotherapeutic agent. The aim of this study was to assess the cytotoxic potency of gemcitabine in compari...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.12.011
更新日期:2017-02-01 00:00:00
abstract::Vinyl carbamate epoxide (VCO) is believed to be the metabolite of ethyl carbamate (EC) ultimately responsible for its carcinogenic effects. This study investigates the role of glutathione (GSH) in protection against VCO-mediated adduct formation, and the involvement of glutathione S-transferases (GSTs) in detoxificati...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1213
更新日期:1995-11-01 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::Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard and it is of interest to determine the mechanism of their toxicity. Of all the BFRs, 3,3',5,5'-tetrabromobisphenol A (TBBPA) is produc...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.01.035
更新日期:2008-07-01 00:00:00
abstract::Metallothionein (MT), a high-affinity metal-binding protein, is known to detoxicate cadmium and may play an important role in cadmium carcinogenesis. In the rat, the ventral lobe of the prostate is sensitive to cadmium carcinogenesis, while the dorsolateral lobe is refractory. The possibility exists that the basis of ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1097
更新日期:1995-05-01 00:00:00
abstract::Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.12.026
更新日期:2009-03-15 00:00:00
abstract::Depression is one of the most common psychiatric disorders in the world. Andrographolide is a natural product that displays evident anti-inflammatory activities. The purpose of the present study was to explore the antidepressant potential of andrographolide in chronic unpredictable mild stress (CUMS)-induced depressiv...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114688
更新日期:2019-09-15 00:00:00
abstract::Cardiotoxin-III (CTX-III), a major cardiotoxin isolated from the venom of the Taiwan cobra (Naja naja atra), is a highly basic, hydrophobic, toxic protein, which can induce lysis of mononuclear cells by an unknown mechanism. This study was undertaken to investigate the effects of CTX-III on untreated and PHA-activated...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(03)00327-2
更新日期:2003-11-15 00:00:00
abstract::Induction of hepatic UDP-glucuronyltransferase(s) (hUDP-GT(s] activity toward thyroid hormones and the relationship between the activity and the serum thyroid hormones or the thyroid stimulating hormone (TSH) level were examined in male Sprague-Dawley rats after four consecutive ip doses of various hepatic enzyme indu...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90138-5
更新日期:1991-10-01 00:00:00
abstract::Exposure protocols were designed to ask whether lung damage in rats exposed to either ozone or nitrogen dioxide is proportional to dose rate or to cumulative dose. Thus, the response of rats to a constant product of concentration of oxidant air pollutant and time of exposure (C x T) was evaluated for 3-day exposures o...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(92)90281-v
更新日期:1992-01-01 00:00:00
abstract::Lung toxicity induced by sulfur mustard is associated with inflammation and oxidative stress. To elucidate mechanisms mediating pulmonary damage, we used 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. Male mice (B6129) were treated intratracheally with CEES (3 or 6 mg/kg) or control. Animals were...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.10.027
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agen...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.09.011
更新日期:2011-12-01 00:00:00
abstract::Geogenic dust from arid environments is a possible inhalation hazard for humans, especially when using off-road vehicles that generate significant dust. This study focused on immunotoxicological and neurotoxicological effects following subacute exposure to geogenic dust generated from sediments in the Nellis Dunes Rec...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.05.017
更新日期:2016-08-01 00:00:00
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::The immunotoxic effects of the environmental carcinogen benzo[a]pyrene (BaP) have been evaluated using mouse, but not human, lymphocytes. Since susceptibility to immunomodulation by BaP may be species-related, the effects of BaP on human peripheral blood mononuclear cells (HPBMC) from several individuals were investig...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1057
更新日期:1993-04-01 00:00:00
abstract::The cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene (CHB), a known in vitro metabolite of the human carcinogen 1,3-butadiene, have not previously been investigated. Because CHB can be bioactivated by alcohol dehydrogenases to yield 1-chloro-3-buten-2-one (CBO), a bifunctional alkylating age...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.04.019
更新日期:2013-08-15 00:00:00
abstract::Two members of the cytochrome P450 2A subfamily, CYP2A10 and 2A11, are abundant nasal enzymes previously characterized in rabbit olfactory microsomes. Rabbit CYP2A is active toward a number of nasal toxicants, including the rat nasal procarcinogen hexamethylphosphoramide (HMPA). While P450s immunochemically related to...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.7975
更新日期:1997-01-01 00:00:00
abstract::Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184mg phorate/kg bw for 14days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.12.006
更新日期:2012-02-15 00:00:00
abstract::A single, intravenous administration of a low dose of monocrotaline pyrrole (MCTP), a derivative of the pyrrolizidine alkaloid monocrotaline (MCT), induces progressive pulmonary hypertension and right ventricular hypertrophy (RVH) in rats. The temporal relationship between morphologic alterations, biochemical markers ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90239-q
更新日期:1990-11-01 00:00:00
abstract::Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has eme...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2015.12.014
更新日期:2016-05-15 00:00:00
abstract::Poly(amidoamine) (PAMAM) dendrimer nanoparticles have been demonstrated to elicit a well defined cytotoxicological response from mammalian cell lines, the response increasing systematically with dendrimer generation and number of surface amino groups. In this work, using generation G4, G5, and G6 dendrimers, this syst...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.08.016
更新日期:2010-11-01 00:00:00
abstract::Morphine has been shown to reduce renal and hepatic clearance of several xenobiotics in rodents. After iv administration of gentamicin, 10 to 30 mg/kg, its plasma levels were elevated in mice given morphine, 20 mg/kg sc. Plasma clearance of gentamicin was nearly halved by morphine, due primarily to lowering of the eli...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90044-0
更新日期:1988-05-01 00:00:00
abstract::Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondria...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.11.001
更新日期:2015-01-01 00:00:00
abstract::All nutritional selenium sources are transformed into the assumed common intermediate selenide for the syntheses of selenoproteins for utilization and/or of selenosugar for excretion. Methylselenol [monomethylselenide, MMSe] is the assumed intermediate leading to other methylated metabolites, dimethylselenide (DMSe) a...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.09.011
更新日期:2008-01-15 00:00:00
abstract::Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA dama...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.08.013
更新日期:2010-11-15 00:00:00