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 the liver, many tumor promoters induce cytochrome P450 enzymes and other proteins in centrilobular cells at much lower doses than required to cause induction in periportal cells. In addition, these induction responses appear to occur at the level of individual cells--a 50% response of the liver for induction does not represent 50% induction in all cells. Instead, half of the cells are fully induced and half are unaffected. Cells "switch" from one phenotypic state to another. Over the past 10 years, several attempts have been made to model these cellular switches and to understand their relevance for hepatic tumor promotion and risk assessment. The data used for analyzing these switches include responses of the entire liver (total induction), responses of individual cells in the liver (regional induction), and cellular responses such as proliferation and apoptosis. This brief overview describes the development of biologically based, dose-response (BBDR) models for protein induction and tumor promotion in liver by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with emphasis on the role of specific types of histological and molecular data in providing insights about mechanisms for cellular switches and their implications for tumor promotion. As the biological basis of these switches become unraveled and incorporated into the models, these BBDR models should eventually serve to improve risk assessments with a variety of liver tumor promoters with receptor-based modes of action.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Andersen MEdoi
10.1080/01926230252824789subject
Has Abstractpub_date
2002-01-01 00:00:00pages
106-11issue
1eissn
0192-6233issn
1533-1601journal_volume
30pub_type
杂志文章,评审abstract：:To characterize the hepatic lesions in Fischer 344 (F344) rats afflicted with large granular lymphocyte (LGL) leukemia, the livers of rats with LGL leukemia at various stages were examined histopathologically and immunohistochemically. The morphologic features in the livers of rats afflicted with LGL leukemia were dif...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623315578719
更新日期：2015-08-01 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
doi：10.1177/0192623313503518
更新日期：2014-07-01 00:00:00
abstract：:A significant correlation exists between average daily food consumption and 2-yr survival in control ad libitum (AL)-fed Sprague-Dawley (SD) rats. SD rats were fed Purina Rodent Chow 5002 or a modified chow, 5002-9, with lower protein, fat, metabolizable energy and increased fiber AL or by dietary restriction (DR) to ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339402200308
更新日期：1994-05-01 00:00:00
abstract：:Livers of male Sprague-Dawley rats were evaluated for foci and nodules 90 days and 16 months after one or two oral doses of 1,2-dibromoethane (DBE). Rats (190 g) were given the following oral treatments. Controls received corn oil (2.5 ml/kg) at 0 and 24 hr. DBE X 1 received corn oil at 0 hr and 75 mg DBE/kg at 24 hr....
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262338401200402
更新日期：1984-01-01 00:00:00
abstract：:Recombinant soluble CD4 (sT4) has been shown to inhibit infectivity of HIV. Because of the role CD4 plays in the interaction of T-helper lymphocytes and cells bearing MHC Class II antigens, a potential adverse effect of therapy with sT4 is interference with lymphocyte function. To address this issue, we studied the ef...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339101900403
更新日期：1991-01-01 00:00:00
abstract：:Substantial progress in understanding nongenotoxic or secondary mechanisms of tumorigenesis has been made over the past decade. However, the methods used in regulated studies for assessment of carcinogenic potential in chemicals in development have not evolved significantly. Based on the experience of over 30 yr of te...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1177/019262339602400610
更新日期：1996-11-01 00:00:00
abstract：:The toxicities of 2'-fluorouridine (2'-FU) and 2'-fluorocytidine-HCl (2'-FC) were separately evaluated in 2 species, male Fischer 344 (F334) rats and woodchucks. Particular attention was focused on the ability of these nucleosides to induce toxicities similar to those induced by the antiviral drug fialuridine (FIAU). ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339902700601
更新日期：1999-11-01 00:00:00
abstract：:The 2012 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Boston in advance of the Society of Toxicologic Pathology's 31st annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic patholog...
journal_title：Toxicologic pathology
pub_type：
doi：10.1177/0192623312467102
更新日期：2013-02-01 00:00:00
abstract：:Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623317751573
更新日期：2018-02-01 00:00:00
abstract：:The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262338701500201
更新日期：1987-01-01 00:00:00
abstract：:In vitro techniques for the culture of hemopoietic stem cells and committed hemopoietic progenitor cells in rat bone marrow have not been adequately described in the literature. In the present investigations, and using commercially available hemopoietic cytokines and growth factors, the conditions required to perform ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623308328133
更新日期：2009-02-01 00:00:00
abstract：:Liver resection is a suitable option for the treatment of certain hepatic conditions, particularly hepatocarcinomas, in patients with cirrhosis. However, this disease impairs liver regeneration, which increases the risk of liver failure and postoperative death. Supportive treatments for regeneration of the remaining l...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623313486316
更新日期：2014-01-01 00:00:00
abstract：:Benzene is of particular concern because of recent research indicating that benzene exposure can result in toxicity. The hematotoxic effect of benzene is mentioned. However, there is little knowledge about the correlation between the biomarker of benzene exposure and changes in red blood cell parameters. Here, the cor...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230601156278
更新日期：2007-02-01 00:00:00
abstract：:Chlorozotocin is a chloroethylnitrosourea antitumor agent that is in clinical trial for a variety of human tumors. Renal failure has been a reported side effect of treatment with several of the chloroethylnitrosoureas, including chlorozotocin. To better understand the pathogenesis of this target organ toxicity, we hav...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262338601400211
更新日期：1986-01-01 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
pub_type： 杂志文章
doi：10.1177/019262338501300305
更新日期：1985-01-01 00:00:00
abstract：:The prevalence of liver and skin tumors in brown bullhead ( Ameiurus nebulosus) from the Anacostia River (Washington, DC) and nearby areas was determined in 2014, 2015, and 2016. The objectives were to (1) compare tumor prevalence across space and time; (2) analyze the 1992-2016 Chesapeake Bay Tumor Database to identi...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623318823150
更新日期：2019-02-01 00:00:00
abstract：:Selenoprotein P is an abundant extracellular protein that is expressed in liver, brain, and other tissues. Studies in mice with the selenoprotein P gene deleted (Sepp-/- mice) have implicated the protein in maintaining brain selenium. Sepp-/- mice fed a normal or low selenium diet develop severe motor impairment and d...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230500243045
更新日期：2005-01-01 00:00:00
abstract：:In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand ...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230600695474
更新日期：2006-01-01 00:00:00
abstract：:The 2019 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Raleigh, North Carolina, at the Society of Toxicologic Pathology's 38th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This ar...
journal_title：Toxicologic pathology
pub_type：
doi：10.1177/0192623319876929
更新日期：2019-12-01 00:00:00
abstract：:Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate are used to treat dyslipidemia. Although fenofibrate is considered safe in humans, it is known to cause hepatocarcinogenesis in rodents. To evaluate untargeted metabolic profiling as a tool for gaining insight into the underlying...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623309336152
更新日期：2009-06-01 00:00:00
abstract：:Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorat...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623317721748
更新日期：2017-07-01 00:00:00
abstract：:The title of the 2016 Society of Toxicologic Pathology (STP) Symposium was the "Basis and Relevance of Variation in Toxicologic Responses." Many factors may contribute to variation in toxicologic responses and can confound results, complicate interpretation of data, interfere with reproducibility, and make extrapolati...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623316675765
更新日期：2017-01-01 00:00:00
abstract：:Weak peroxisome proliferator-activated receptor (PPAR) α agonists (fibrates) are used to treat dyslipidemia. This study compared the effects of the potent and selective PPARα agonist CP-778875 on peroxisomal β-oxidation and cardiac and/or skeletal muscle injury with those of the weak PPARα agonist fenofibrate. We hypo...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/0192623311431945
更新日期：2012-04-01 00:00:00
abstract：:To explore the hypothesis that air pollution promotes cardiovascular changes, Swiss mice were continuously exposed, since birth, in two open-top chambers (filtered and nonfiltered for airborne particles journal_title：Toxicologic pathology pub_type： 杂志文章 doi：10.1177/0192623309332994 更新日期：2009-04-01 00:00:00
abstract：:Microcystin-LR (MCLR) is an acute hepatotoxicant and suspected carcinogen. Previous chronic studies have individually described hepatic morphologic changes, or alterations in the cytoskeleton, cell signaling or redox pathways. The objective of this study was to characterize chronic effects of MCLR in wild-type mice ut...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1080/01926230701383210
更新日期：2007-06-01 00:00:00
abstract：:Sections of thymus from New Zealand white rabbits used as controls in 28-day and 91-day percutaneous toxicity studies conducted at different laboratories were morphometrically assessed. Measurements of total thymic area, medullary area, and cortical area were greater for 28-day vs 91-day studies conducted at a given l...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339001800307
更新日期：1990-01-01 00:00:00
abstract：:Historical control tumor data are useful in the interpretation of long-term rodent carcinogenicity bioassays, especially to assess the occurrence of rare tumors and marginally increased tumor incidences. The major prerequisites to compare historical control data with studies under evaluation are the validity and consi...
journal_title：Toxicologic pathology
pub_type： 杂志文章,评审
doi：10.1080/01926230252824743
更新日期：2002-01-01 00:00:00
abstract：:Groups of 5 male beagle dogs were treated orally with hydralazine tablets in gelatin capsules at a dose of 12 or 24 mg/kg twice a day (6 hours apart) for 2 consecutive days. Five male dogs treated with empty gelatin capsules served as untreated controls. Clinical findings and heart rate changes during treatment and te...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262338701500404
更新日期：1987-01-01 00:00:00
abstract：:Recent advances in immunocytochemical techniques allow the localization of specific antigens in tissue sections. The work reported here attempts to evaluate the application of antibody-labeled, disease-related protein, followed by microscopy and computerized image analysis. Using an experimental anti-tumor, polyclonal...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262338701500308
更新日期：1987-01-01 00:00:00
abstract：:To clarify the cell of origin of granular cell tumors in the rat brain, light and/or electron microscopic examinations were performed on 40 cases of spontaneous meningeal tumors in Wistar (Jcl: Wistar) rats. The meningeal tumors were histologically subclassified into 3 types: meningothelial meningiomas (MMs), 3 cases;...
journal_title：Toxicologic pathology
pub_type： 杂志文章
doi：10.1177/019262339702500211
更新日期：1997-03-01 00:00:00
