Abstract:
:Developmental exposure to estrogenic chemicals is an established risk factor for cancer of the female reproductive tract. This increase in risk has been associated with disruption of normal patterns of cellular differentiation during critical stages of morphogenesis. The goal of this study was to document uterine epithelial phenotypes over time following neonatal treatment with the synthetic estrogen diethylstilbestrol (DES) or the soy phytoestrogen genistein (GEN) in female CD-1 mice. Both DES and GEN induced three distinct populations of abnormal endometrial epithelial cells: luminal (SIX1+/P63-/CK14-/CK18+), basal (SIX1+/P63+/CK14+/CK18-), and mixed/bipotential (SIX1+/P63-/CK14+/CK18+), which were all established by early adulthood. In older animals, DES and GEN resulted in uterine carcinomas with mixed glandular, basal, and squamous cell elements. All carcinomas were composed largely of the three abnormal cell types. These findings identify novel epithelial differentiation patterns in the uterus and support the idea that disruption of cellular programming in early development can influence cancer risk later in life.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Suen AA,Jefferson WN,Williams CJ,Wood CEdoi
10.1177/0192623318779326subject
Has Abstractpub_date
2018-07-01 00:00:00pages
574-596issue
5eissn
0192-6233issn
1533-1601journal_volume
46pub_type
杂志文章abstract::Our previous studies showed that protein kinase Cepsilon (PKCepsilon) verexpression in mouse skin resulted in metastatic squamous cell carcinoma (SCC) elicited by single 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion in the absence of preceding papilloma forma...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230701748164
更新日期:2007-12-01 00:00:00
abstract::This is a survey of the results of recent investigations on gastrointestinal (GI) peptide hormones. In addition to the classical GI hormones (secretin, gastrin, and cholecystokinin-pancreozymin (CCK-PZ], there are at least nine other peptides whose structures and GI effects are known. These include vasoactive intestin...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338801600203
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abstract::There has been a substantial increase in the number and efficacy of laboratory biomarkers for the evaluation of human cardiac injury over the last decade. The advantages of these over traditional laboratory tests have encouraged adoption of comparable markers in nonclinical studies for cardiac injury assessment. Of pa...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230500519816
更新日期:2006-01-01 00:00:00
abstract::Excitatory amino acids (EAAs) mediate their effects through the glutamate receptors (GluRs) in the brain. GluRs play an important role in the treatment of a variety of neuropsychiatric conditions and are central to the neurotoxicity of EAAs such as domoic and kainic acid. Unstained histological preparations of human h...
journal_title:Toxicologic pathology
pub_type: 杂志文章
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更新日期:2007-04-01 00:00:00
abstract::Novel urinary protein biomarkers for the detection of acute renal damage, recently accepted by the U.S. Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency (Japan), now have to be validated in practice. Limited data regarding the performance of these acute markers af...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623312444618
更新日期:2012-10-01 00:00:00
abstract::Two-year toxicity studies were conducted on the widely used herbal products, goldenseal and milk thistle, in male and female F344/N rats and B6C3F1 mice. With goldenseal root powder, the primary finding was an increase in liver tumors in rats and mice, and with milk thistle extract, a decrease in spontaneous backgroun...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310394211
更新日期:2011-02-01 00:00:00
abstract::Alanine aminotransferase (ALT) is used as an indicator of hepatocellular injury. Since ALT consists of two isoenzymes, a better understanding of ALT isoenzyme biology in response to compounds that cause metabolic adaptive versus hepatotoxic responses will allow for a more accurate assessment of the significance of an ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623312447550
更新日期:2012-12-01 00:00:00
abstract::The development process of myelination varies between region and species. Fully myelinated fibers are required if mammalian neural circuits are to function normally. Histology samples at staggered time points throughout the study were examined at days 4, 5, 7, 8, 10, 14, 17, 24, 37, and 44. We suggest that the develop...
journal_title:Toxicologic pathology
pub_type: 杂志文章
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abstract::During preclinical investigations into the safety of drugs and chemicals, many are found to interfere with reproductive function in the female rat. This interference is commonly expressed as a change in normal morphology of the reproductive tract or a disturbance in the duration of particular phases of the estrous cyc...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
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更新日期:2008-04-01 00:00:00
abstract::Furan is a potent cholangiocarcinogen in rat by an as yet undefined mechanism. The risk to man remains unclear. Using a time-course stop study design, we have investigated the potential of furan to induce oxidative stress and DNA damage associated with inflammatory and regenerative responses in rat liver. Furan was ad...
journal_title:Toxicologic pathology
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更新日期:2010-02-01 00:00:00
abstract::Investigations in toxicologic neuropathology are complex undertakings because of the intricate spatial and temporal diversity in the anatomic, functional, and molecular organization of the central and peripheral nervous systems. This compilation of toxicologic neuropathology resources has been designed to consolidate ...
journal_title:Toxicologic pathology
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更新日期:2011-01-01 00:00:00
abstract::A compendium of carcinogenesis bioassay results organized by target organ is presented for 738 chemicals that are carcinogenic in chronic-exposure, long-term bioassays in at least 1 species. This compendium is based primarily on experiments in rats or mice; results in hamsters, monkeys, and dogs are also reported. The...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/019262301753385979
更新日期:2001-11-01 00:00:00
abstract::Aroclor 1254, at a dose level of 280 micrograms/kg body weight equivalent to 200 micrograms/kg/day, was given 5 days per week to rhesus monkeys over a 27 to 28 month period. Terminal clinical signs of varying severity included fingernail detachment, exuberant nail beds, weight loss, stomatitis and normocytic anemia. A...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400101
更新日期:1986-01-01 00:00:00
abstract::The 2018 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Indianapolis, Indiana, at the Society of Toxicologic Pathology's 37th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This arti...
journal_title:Toxicologic pathology
pub_type:
doi:10.1177/0192623318800734
更新日期:2018-12-01 00:00:00
abstract::We examined the effects of the quinolone antibacterial agents pefloxacin (PFLX) and ofloxacin (OFLX) on the Achilles tendon of Sprague-Dawley rats. A single oral administration of PFLX 300 and 900 mg/kg or OFLX 900 mg/kg induced edema with mononuclear cell infiltration mainly in the inner sheath of the inner Achilles ...
journal_title:Toxicologic pathology
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doi:10.1177/019262339502300315
更新日期:1995-05-01 00:00:00
abstract::Morphologic lesions have received only limited attention as in vitro endpoints of toxicity. In the present work, "tissue" and cell morphology of control and toxicant-treated primary dissociated cerebrocortical cell cultures from fetal mice were examined using phase-contrast and bright-field microscopy. In untreated co...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100506
更新日期:1993-09-01 00:00:00
abstract::In organs with diverse cell populations, it is not uncommon for one type of cell to respond while others are spared. Even in an organ with common cell types, such as hepatocytes within the liver, the population of cells may respond with different sensitivities for injury or for biochemical responses to toxicants. In t...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230252824789
更新日期:2002-01-01 00:00:00
abstract::Sialodacryoadenitis (SDA) is a commonly-encountered coronaviral infection in laboratory rats that causes acute destruction of submandibular salivary glands. SDA results in depletion of salivary epidermal growth factor (EGF) and may thereby affect EGF-dependent cell growth processes. The purpose of this study was to de...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339101900210
更新日期:1991-01-01 00:00:00
abstract::Carcinogenicity testing of antitumor agents in animal bioassays has been proposed because of the potential for carcinogenicity of this class of agents and the expectation that such testing may indicate prospectively the target organs of any related human oncogenesis. The literature reveals the anticipated confirmation...
journal_title:Toxicologic pathology
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abstract::After 15 years of existence, the ACVP/STP Coalition for Veterinary Pathology Fellows will dissolve, primarily due to lack of renewed financial sponsorship. While in operation, the Coalition organized 32 new training position for veterinary pathologists, supported by $7.4 M from sponsors, including pharmaceutical and b...
journal_title:Toxicologic pathology
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更新日期:2020-06-01 00:00:00
abstract::Reticulum cell hyperplasia (RCH) was a term used for many years by the National Toxicology Program (NTP) to describe a certain non-neoplastic bone marrow lesion of rats. Retrospective microscopic evaluation of RCH lesions and immunohistochemistry analyses were performed to reassess and further characterize these lesio...
journal_title:Toxicologic pathology
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abstract::A review of the data obtained from various studies on carcinogenicity of vinyl chloride (VC) in rodents, particularly on the effect of dose, age, duration of exposure and potential reversibility of lesions, revealed that vinyl chloride-induced carcinogenicity in rodents was dose and time related; no recovery occurred ...
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更新日期:1983-01-01 00:00:00
abstract::d-galactosamine (d-GalN) is a well-known hepatotoxic agent that causes liver injury. Conversely, hepatic macrophages play a crucial role in maintaining liver tissue integrity. Macrophage functions were investigated in hepatic lesions induced by a single intraperitoneal injection of d-GalN (800 mg/kg body weight [BW]) ...
journal_title:Toxicologic pathology
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更新日期:2018-10-01 00:00:00
abstract::Nephrotoxicity is one of the more common causes of attrition in nonclinical drug development. Like most tissues, the kidney has a limited number of ways of responding to toxicological insults from diverse mechanistic pathways, which can limit the ability to determine mechanisms of renal injury using the assays routine...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318788302
更新日期:2018-08-01 00:00:00
abstract::Mixed-function oxidase (MFO) induction in the mouse liver results in a rapid and sustained centrilobular hypertrophy associated with a hyperplastic response. In many studies, the long-term sequela of prolonged exposure is an increased incidence of lesions considered to be adenomas. Studies have shown in aged control m...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339602400411
更新日期:1996-07-01 00:00:00
abstract::In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrach...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200118
更新日期:1984-01-01 00:00:00
abstract::Although the dog is a common choice among nonrodent species in evaluation of compound safety for regulatory submission, information regarding the incidence of spontaneous or incidental microscopic changes in canine peripheral nerve is limited. A retrospective examination was performed of routine histologic preparation...
journal_title:Toxicologic pathology
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更新日期:2011-08-01 00:00:00
abstract::Minoxidil, a long-acting vasodilating antihypertensive agent, reduces arterial blood pressure by a direct action on arteriolar smooth muscle. The present studies examined the gross anatomic, histologic and ultrastructural myocardial alterations produced by 2 daily doses of minoxidil in beagle dogs (0.5, 1, or 3 mg/kg)...
journal_title:Toxicologic pathology
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更新日期:1989-01-01 00:00:00
abstract::Fusion of biologic therapeutics to hyaluronic acid binding proteins, such as the link domain (LD) of Tumor necrosis factor (TNF)-Stimulated Gene-6 (TSG-6), is expected to increase vitreous residence time following intravitreal injection and provide for long-acting delivery. The toxicity of a single intravitreal dose o...
journal_title:Toxicologic pathology
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更新日期:2020-12-21 00:00:00
abstract::The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO3 was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which re...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339702500306
更新日期:1997-05-01 00:00:00