Abstract:
:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD),12 the most toxic congener of dioxins, exhibits wide sensitivity differences between a sensitive Long-Evans (L-E) rat and a resistant Han/Wistar (H/W) rat. The sensitivity is determined probably by two autosomal genes and it is highly end point dependent. The difference is more than 1000-fold for acute toxicity and negligible for CYP1A1 induction. The rat strains were recently shown to have differences in the size of AH receptor (AHR), which mediates most effects of TCDD. In the present study, the rat strains were crossed and the resistant alleles of genes determining TCDD sensitivity were segregated to new rat lines. Selection was based on AHR phenotype determined by Western blot and resistance to TCDD lethality. Two genes determining resistance were found: the Ahr and a novel gene designated "B." In homozygous rats, the H/W type Ahrhw allele prevented TCDD lethality up to 2000 microg/kg or more, and the H/W type "Bhw" allele also increased resistance to TCDD lethality but to a lesser extent. Heterozygous rats were only slightly more resistant to acute lethality than the respective sensitive homozygous rats. CYP1A1 induction was similar irrespective of the Ahr and "B" genotypes, but a substantial increase in serum bilirubin seen after low doses in sensitive rats occurred only after large doses in "Bhw/hw" and not at all in Ahrhw/hw rats. In conclusion, the Ahrhw allele is a major determinant of the exceptional resistance of H/W rats to TCDD lethality. There is also an additional gene, whose function remains to be characterized, conferring limited resistance to TCDD toxicity. These two H/W rat-derived alleles are separately expressed in the new rat lines created.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Tuomisto JT,Viluksela M,Pohjanvirta R,Tuomisto Jdoi
10.1006/taap.1998.8564subject
Has Abstractpub_date
1999-02-15 00:00:00pages
71-81issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(98)98564-7journal_volume
155pub_type
杂志文章abstract::p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; 75 mg/kg) or corn oil was administered po to male Fischer 344N rats. Tremor was quantified 8 hr later by spectral analysis of whole body movements. The effect of sc injection of pharmacological challenges on the spectral profile of body movements was determined....
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90096-2
更新日期:1987-11-01 00:00:00
abstract::A study was undertaken to determine whether alterations in the gene expression or overt histological signs of neurotoxicity in selected regions of the forebrain might occur from acrylamide exposure via drinking water. Gene expression at the mRNA level was evaluated by cDNA array and/or RT-PCR analysis in the striatum,...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.07.036
更新日期:2009-11-01 00:00:00
abstract::Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.10.008
更新日期:2012-12-01 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::Previous studies from this laboratory have demonstrated that the addition of methyl groups at the 3 and 4 positions of the 2,5-hexanedione (2,5-HD) molecule results both in more rapid pyrrole formation and in enhanced neurotoxicity. In order to define more clearly the relationship between rates of pyrrole formation an...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90296-1
更新日期:1987-02-01 00:00:00
abstract::Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot stu...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.05.020
更新日期:2006-10-15 00:00:00
abstract::A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.09.006
更新日期:2013-09-15 00:00:00
abstract::Exposure of intact cultured Chinese hamster ovary (CHO) cells to water-soluble nickel (Ni) salts and to relatively water-insoluble crystalline nickel subsulfide (Ni3S2) resulted in an increased formation of the fluorescent oxidized compound, dichlorofluorescein (DCF) from the parent nonfluorescent compound, 2,7-dichlo...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1083
更新日期:1993-05-01 00:00:00
abstract::Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen sign...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.08.013
更新日期:2016-10-01 00:00:00
abstract::Exposure to airborne particulate matter (PM) is associated with increased mortality and morbidity. It has been previously shown that PMs and synthetic particles (PC10 and PC2) that have similar characteristics to PMs induced depolarizing currents and increases in intracellular calcium ([Ca2+]i) in capsaicin- and acid-...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(03)00259-x
更新日期:2003-10-01 00:00:00
abstract::We have previously shown that ricin, a toxic lectin from the castor bean, increases cardiac output and blood flow to the heart in rabbits in the early stage of its intoxication and causes hemorrhage and necrosis in the heart following a lethal dose. To investigate possible alterations in coronary arteries following ri...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1994.1224
更新日期:1994-11-01 00:00:00
abstract::The effects of low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male offspring rats were examined. The dams were treated subcutaneously 2 weeks prior to mating and throughout mating, pregnancy, and lactation. They received an initial loading dose of 25, 60, or 300 ng TCDD/kg body w...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8433
更新日期:1998-06-01 00:00:00
abstract::Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2012.05.007
更新日期:2012-08-01 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::Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and beta-carotene, on peroxyni...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.03.006
更新日期:2006-09-15 00:00:00
abstract::The anticancer drug ellipticine exerts its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. The present study has examined the role of cytochrome P450 oxidoreductase (POR) and cytochrome b5 (Cyb5), electron donors to P450 enzymes, in the CYP-mediated metabolism and disposition of elliptic...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.01.020
更新日期:2019-03-01 00:00:00
abstract::Infants exposed to second hand smoke (SHS) experience more problems with wheezing. This study was designed to determine if perinatal SHS exposure increases intrinsic and/or in vivo airway responsiveness to methacholine and whether potential structural/cellular alterations in the airway might explain the change in resp...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.10.018
更新日期:2009-02-01 00:00:00
abstract::Spontaneous activity represents an early, primitive form of motor activity within zebrafish embryos, providing a potential readout for identification of neuroactive compounds. However, despite use as an endpoint in chemical screens around the world, the predictive power and limitations of assays relying on spontaneous...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2017.06.011
更新日期:2017-08-15 00:00:00
abstract::There is a subpopulation of the CF-1 mouse strain that is very sensitive to the neurotoxicity induced by the avermectins, a class of natural products widely used in veterinary and human medicine as anti-parasitic agents. This sensitivity results from a lack of P-glycoprotein in the intestine and brain of sensitive ani...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8225
更新日期:1997-09-01 00:00:00
abstract::A clinical study was performed to determine the effects of patch testing human skin with four industrially used surfactants on erythema formation, transepidermal water loss, and the contents in suction blister fluids of primary proinflammatory mediators including arachidonic acid, eicosanoids, and IL-1 alpha, which we...
journal_title:Toxicology and applied pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1006/taap.1998.8521
更新日期:1998-11-01 00:00:00
abstract::Lovastatin (LOVA) is a potent inhibitor of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase widely used in clinical practice. We treated primary cultures of adult rat hepatocytes, maintained in a minimal, serum-free medium on Matrigel, a reconstituted basement membrane, with this drug, and found that the amounts of P450...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1115
更新日期:1993-06-01 00:00:00
abstract::Although carbon tetrachloride (CCl4) is of concern as a drinking water contaminant, it has been necessary in most oral toxicity studies to give CCl4 in an oil vehicle due to its limited water solubility. The primary objective of our study was to assess the influence of dosing vehicles on the acute hepatotoxicity of CC...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90081-5
更新日期:1990-01-01 00:00:00
abstract::Methylmercury (MeHg) is an ubiquitous environmental pollutant which is transported into the mammalian cells when present as the methylmercury-cysteine conjugate (MeHg-Cys). With special emphasis on hepatic cells, due to their particular propensity to accumulate an appreciable amount of Hg after exposure to MeHg, this ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.01.010
更新日期:2011-04-01 00:00:00
abstract::Oxido-inflammatory aberrations play a substantial role in the pathophysiology of depression. Oxido-inflammatory stress increases catabolism of tryptophan into kynurenine which leads to imbalance in kynurenine and serotonin levels in the brain. Naringenin a flavonoid, has been reported to possess antidepressant propert...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2018.07.010
更新日期:2018-09-15 00:00:00
abstract::The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. T...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2014.04.013
更新日期:2014-07-01 00:00:00
abstract::A major obstacle in defining the mechanism of chemical-induced toxicity has been the inability to distinguish between events that cause cell death and those that result from cell death. This problem results from measuring biochemical parameters in tissues or cell pellets containing both viable and nonviable cells. In ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90350-3
更新日期:1985-06-30 00:00:00
abstract::In rat skeletal muscle, chronic exposure to 50 ppm Cd2+ in drinking water produced both ultrastructural and functional damage, which took place successively and increased gradually with duration of treatment. Ultrastructurally, the first effect was a regression of the sarcoplasmic reticulum, mitochondrial cristae, and...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90264-9
更新日期:1985-01-01 00:00:00
abstract::Some widely used psychoactive drugs, such as tricyclic antidepressants and antipsychotic phenothiazines exhibit iatrogenic effects on the thyroid. These side effects may arise from interactions at different steps of thyroid hormone biosynthesis. These drugs can induce a change in iodine capture by thyroid cells or can...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1006/taap.1998.8367
更新日期:1998-04-01 00:00:00
abstract::Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of >90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2μg/kgbw/d (25th-95th percentil...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.07.009
更新日期:2011-09-15 00:00:00
abstract::The neurotoxicity of the dl and meso diastereomers of the gamma-diketone 3,4-dimethyl-2,5-hexanedione (DMHD) was studied to determine if the difference in rates of pyrrole derivatization would influence the clinical and morphological appearance of the neuropathy associated with these gamma-diketones. Two groups of rat...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90297-3
更新日期:1987-02-01 00:00:00