Abstract:
:The effects of structure on the estrogenicity and antiestrogenicity of hydroxylated polychlorinated biphenyls were investigated using the following estrogen-sensitive assays: competitive binding to the rat and mouse cytosolic estrogen receptor (ER); immature rat and mouse uterine wet weight, peroxidase and progesterone receptor (PR) levels; induction of luciferase activity in HeLa cells stably transfected with a Gal4:human ER chimera and a 17mer-regulated luciferase reporter gene; proliferation of MCF-7 human breast cancer cells; induction of chloramphenicol acetyl transferase (CAT) activity in MCF-7 cells transiently transfected with a full-length human ER expression plasmid and a plasmid containing an estrogen-responsive vitellogenin A2 promoter linked to a CAT reporter gene. The chemicals synthesized for this study contained a 4-hydroxy group in one ring, a 2- or 3-chloro substituent meta or ortho to the hydroxyl group, and variable substitution (2',3',4',5'-, 2',3',4',6'-, 2',3',5',6'-tetrachloro and 2',4',6'-trichloro) in the chlorophenyl ring. The compounds included: 2,2',3',4',5'- (A), 2,2',3',4',6'- (B), and 2,2',3',5',6'-pentachloro- (C); 2,2',4',6'-tetrachloro-4-biphenylol (D); 2',3,3',4',5'- (E), 2',3,3',4',6'- (F), and 2',3,3',5',6'-pentachloro (G); and 2',3,4',6'-tetrachloro-4-biphenylol (H). With the exception of 2',3,4',6'-tetrachloro-4-biphenylol (H), all of the compounds competitively bound to the mouse and rat ER with relative binding affinities [compared to 17beta-estradiol (E2)] varying from 1.4 x 10(-3) to 5.3 x 10(-5). The structure-ER binding relationships for the hydroxy-PCB congeners were different in the rat and mouse, and no dose-dependent estrogenic activities were observed in the mouse or rat uterus. Several hydroxy-PCB congeners exhibited antiestrogenic activity (primarily in the mouse uterus) and two compounds, 2,2',3',5',6- and 2,2',3',4',6'-pentachloro-4-biphenylol, inhibited E2-induced uterine wet weight, PR binding, and peroxidase activity in the mouse uterus. 2,2',3',4',5'- and 2,2',3',4',6'-Pentachloro-4-biphenylol induced CAT activity in MCF-7 cells transiently transfected with the Vit-CAT plasmid; the remaining congeners did not induce CAT activity but exhibited antiestrogenic activity in MCF-7 cells cotreated with 10(-9) E2 plus 10(-5) M hydroxy-PCBs. Complementary structure-estrogenicity relationships were observed utilizing the HeLa cell luciferase induction and MCF-7 cell proliferation assays. The placement of the 2- or 3-chloro groups in the phenolic ring had minimal effects on estrogenic activity, whereas 2,4,6-trichloro- and 2,3,4,6-tetrachloro substitution in the chlorophenyl ring (B, D, F, and H) were required for this response. Substitution in the phenolic ring was also not important for structure-antiestrogenicity relationships, and the most active compounds (A, C, E, and G) contained 2',3',4',5'- and 2',3',5',6'-tetrachlorophenyl groups. Thus, structure-estrogenicity/antiestrogenicity relationships for this series of hydroxy-PCBs were complex and response-specific.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Connor K,Ramamoorthy K,Moore M,Mustain M,Chen I,Safe S,Zacharewski T,Gillesby B,Joyeux A,Balaguer Pdoi
10.1006/taap.1997.8169subject
Has Abstractpub_date
1997-07-01 00:00:00pages
111-23issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(97)98169-2journal_volume
145pub_type
杂志文章abstract::In this study, the mouse was used to evaluate paternal germline exposure to the organophosphate methamidophos for its potential to produce adverse effects on spermatozoa and in the offspring. There have been reports that organophosphate exposure can increase abnormal sperm morphology in mice. However, effects transmit...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2000.8933
更新日期:2000-06-01 00:00:00
abstract::The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effec...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.08.024
更新日期:2013-11-15 00:00:00
abstract::Trichloroethene (TCE) has been implicated in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and scleroderma in humans. However, experimental studies have not been conducted to establish the role of TCE in causing autoimmunity and/or SLE. To clarify the role of TCE in autoimmune resp...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1179
更新日期:1995-09-01 00:00:00
abstract::Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90117-8
更新日期:1989-06-01 00:00:00
abstract::We examined interactions in rats between NO2 gas and respirable aerosols of sulfuric acid (H2SO4) or sodium chloride (NaCl). Rats were exposed for 1, 3, or 7 days to 5 ppm of NO2 gas, alone or in combination with 1 mg/m3 of H2SO4 or NaCl aerosols. The apparent rate of collagen synthesis by lung minces was measured aft...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90303-6
更新日期:1987-08-01 00:00:00
abstract::Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2006.10.013
更新日期:2007-01-01 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::Allergic contact dermatitis (ACD) is caused by topical exposure to chemical allergens. Keratinocytes play a key role in innate immunity, as well as in ACD progression. The transmembrane Toll-like receptor 4 (TLR4), strongly implicated in skin inflammation, has the ability to bind Damage Associated Molecular Patterns (...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114632
更新日期:2019-08-15 00:00:00
abstract::Interleukin-6 (IL-6) is a central mediator of immunotoxicity that is associated with exposure to the trichothecene vomitoxin (VT). The purpose of this investigation was to test the hypothesis that the inducible cyclooxygenase-2 (COX-2) and its metabolites contribute to VT-induced IL-6 upregulation. VT at 100 to 250 ng...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(02)00033-9
更新日期:2003-03-01 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::Gap junctional intercellular communication appears to be important in the regulation of cellular homeostasis, differentiated cell functions, and growth control in adult tissues. Interruption of intercellular communication by chemical compounds has been shown to be a sublethal response to a number of tumor promoters. T...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90050-5
更新日期:1990-03-01 00:00:00
abstract::Ethylnitrosourea (ENU) is a proven animal teratogen, although the mechanism of its developmental toxicity is unknown. The micromass rat embryo midbrain (CNS) and limb bud (LB) cultures were used in an effort to determine potential mechanisms by which ENU may exert its teratogenic effect. When cultured at high cell den...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90295-6
更新日期:1990-06-15 00:00:00
abstract::We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response cu...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.11.014
更新日期:2006-07-01 00:00:00
abstract::The epithelial-mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leadin...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.01.010
更新日期:2016-03-01 00:00:00
abstract::The mitochondrial permeability pore is subject to regulation by a thiol-dependent voltage sensor (Petronilli, V., Costantini, P., Scorrano, L., Colonna, R., Passamonti, S., and Bernardi, P., J. Biol. Chem. 269, 16638-16642, 1994); thiol oxidation increases the gating potential, which increases the probability of pore ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.8099
更新日期:1997-04-01 00:00:00
abstract::Erionite, a naturally occurring fibrous zeolite, is associated with the development of nonmalignant and malignant lung diseases and is more carcinogenic than asbestos fibers in man and rodent inhalation models of disease. To investigate the possible molecular mechanisms of erionite-induced toxicity and carcinogenesis ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8450
更新日期:1998-07-01 00:00:00
abstract::The Bcl-2 family contains a panel of proteins which are conserved regulators of apoptosis in mammalian cells, like the anti-apoptotic protein Bcl-2. According to its significant role in altering susceptibility to apoptosis, the deciphering of the mechanism of Bcl-2 expression modulation may be crucial for identifying ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.07.010
更新日期:2011-10-01 00:00:00
abstract::The carcinogenicity prediction and battery selection method was used to predict the probability of carcinogenicity of methyl isocyanate (MIC) based upon the results of short-term tests. The analysis predicts that MIC has a significant potential for inducing cancer in rodents. However, the pattern of response suggests ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90073-1
更新日期:1987-12-01 00:00:00
abstract::The present study was undertaken to evaluate the effects of the chemosterilant 2,4-dinitrotoluene (DNT) on the rat testis. Adult male rats were fed control, or 0.1%, or 0.2% DNT for 3 weeks. An ultrastructural study of the testes was performed, serum was assayed for testosterone and gonadotropins, and sperm reserve co...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90287-6
更新日期:1988-07-01 00:00:00
abstract::Organic cations (OCs) constitute a diverse array of compounds of physiological, pharmacological, and toxicological importance. Renal secretion of these compounds, which occurs principally along the proximal portion of the nephron, plays a critical role in regulating the concentration of OCs in the plasma and in cleari...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2004.10.021
更新日期:2005-05-01 00:00:00
abstract::We report that there is a time-related change in the phospholipase C (PLC) activities of rat brain cytosol and membrane fractions after iv injection of a soman-like or a sarin-like organophosphorous agent (bis(isopropyl methyl)phosphonate [BIMP] and bis(pinacolyl methyl)phosphonate [BPMP]). PLCgamma was activated in t...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8628
更新日期:1999-04-01 00:00:00
abstract::Methyl bromide is used as a disinfectant to fumigate soil and a wide range of stored food commodities in warehouses and mills. Human exposure occurs during the manufacture and use of the chemical. The purpose of this investigation was to determine the disposition and metabolism of [14C]methyl bromide in rats after inh...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90289-3
更新日期:1985-04-01 00:00:00
abstract::Environmental risk assessment requires models for estimating the bioaccumulation of untested compounds. So far, bioaccumulation models have focused on lipophilic compounds, and only a few have included hydrophilic compounds. Our aim was to extend an existing bioaccumulation model to estimate the oral uptake efficiency...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.10.015
更新日期:2013-01-01 00:00:00
abstract::Organic chemicals such as jet fuels and solvents can cause skin irritation after dermal exposure. The molecular responses to these chemicals resulting in acute irritation are not understood well enough to establish safe exposure limits. Male F-344 rats were dermally exposed to JP-8 jet fuel for 1 h using Hill Top Cham...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9248
更新日期:2001-08-15 00:00:00
abstract::The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4nmol) was most potent, reaching 100% tu...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.08.014
更新日期:2012-11-01 00:00:00
abstract::Garlic and its active components are known to possess antioxidant and antiinflammatory effects. The present study investigated the effects of garlic oil and its organosulfur compounds on endotoxin-induced intestinal mucosal damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil (GO), 0.5 mmol/kg...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.08.008
更新日期:2006-05-15 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::The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(03)00274-6
更新日期:2003-10-15 00:00:00
abstract::The physicochemical complexity of airborne particulate matter (PM) has hampered identifying a specific mechanism(s) for its toxicity. In this study, selected physicochemical characteristics (i.e., size, particle number, acidity, and surface charge) were measured on various field PM, derived from urban ambient (St. Lou...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9341
更新日期:2002-02-01 00:00:00
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