Abstract:
:Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3F1 mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell leukemia (50.5%), adrenal gland pheochromocytoma (31.9%), and pituitary gland neoplasms (30.4%). For untreated female F344 rats, the most frequently occurring neoplasms were pituitary gland neoplasms (54.2%), mammary gland fibroadenoma (41.2%), and mononuclear cell leukemia (28.1%). The most frequently occurring neoplasms in untreated male B6C3F1 mice were liver adenoma/carcinoma (42.2%), lung adenoma/carcinoma (20.5%), and malignant lymphoma (8.3%). For untreated female B6C3F1 mice, the most frequently occurring neoplasms were liver adenoma/carcinoma (23.6%), malignant lymphoma (20.9%), and pituitary gland adenoma/carcinoma (14.8%). The tumor rates observed in feeding study (untreated) and inhalation study (chamber) control rats were generally similar. The major exceptions were pituitary gland tumors and testicular adenoma in male F344 rats. The overall incidence of testicular adenoma was much lower in chamber controls (69.4%) than in feeding study controls (89.1%), whereas pituitary gland neoplasm showed the opposite trend (60.7% vs 30.4%). The most likely explanation for this difference is related to the individual housing of chamber controls and the group housing of feeding study controls. Differences in diagnostic criteria may influence reported tumor rates. To ensure consistency and comparability of tumor diagnosis from study to study, the NTP uses rigorous histopathology quality assurance and peer review procedures. Biological factors such as body weight may also affect tumor incidence. For example, increased body weights are associated with increased incidences of certain site-specific neoplasms, especially pituitary gland and mammary gland neoplasms in rats and liver tumors in mice. The presence of Helicobacter hepaticus has been associated with an increased incidence of liver neoplasms in male B6C3F1 mice. Other factors that may produce differences in control tumor rates from study to study include diet, environmental factors, genetic drift, study duration, and survival differences. The NTP database provides historical control data that may be useful in the evaluation of possible chemically related changes in tumor incidence. However, it is essential that the study being evaluated be comparable to those in the NTP database with respect to those factors that are known to influence tumor occurrence.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Haseman JK,Hailey JR,Morris RWdoi
10.1177/019262339802600318subject
Has Abstractpub_date
1998-05-01 00:00:00pages
428-41issue
3eissn
0192-6233issn
1533-1601journal_volume
26pub_type
杂志文章abstract::We believe the development and validation of in vitro alternatives to eliminate the need to use animals in ocular irritation testing must be based on a thorough understanding of the mechanisms of ocular irritation. We have recently undertaken the task of developing such an understanding for a panel of surfactants. The...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600206
更新日期:1998-03-01 00:00:00
abstract::Toxicogenomics using a reference database can provide a better understanding and prediction of toxicity, largely by creating biomarkers that tie gene expression to actual pathology events. During the course of building a toxicogenomic database, an observation was made that a number of non-steroidal anti-inflammatory c...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600611752
更新日期:2006-01-01 00:00:00
abstract::Epidemiological associations have been made between the new onset of childhood rhinitis/asthma and exposures to elevated ambient levels of ozone, a commonly encountered gaseous air pollutant. Our laboratory was the first to find that mice repeatedly exposed to ozone develop nasal type 2 immunity and eosinophilic rhini...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623319873872
更新日期:2019-12-01 00:00:00
abstract::Two-year mouse and rat bioassay studies of 2-methylimidazole (2-MI) conducted by the National Toxicology Program revealed that epididymal sperm granuloma(SG)s occurred only in male B6C3F1 mice in a dose-related manner. The present study characterized 2-MI-induced SGs in these epididymides. Groups of 50 male B6C3F1 mic...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230590922866
更新日期:2005-01-01 00:00:00
abstract::One application of genomics in drug safety assessment is the identification of biomarkers to predict compound toxicity before it is detected using traditional approaches, such as histopathology. However, many genomic approaches have failed to demonstrate superiority to traditional methods, have not been appropriately ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500321213
更新日期:2005-01-01 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::Toxicologists and pathologists worldwide will benefit from a new, website-based, and completely searchable Nonneoplastic Lesion Atlas just released by the U.S. National Toxicology Program (NTP). The atlas is a much-needed resource with thousands of high-quality, zoomable images and diagnostic guidelines for each roden...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313517304
更新日期:2014-01-01 00:00:00
abstract::The Tg.AC mouse is being evaluated for use in short-term carcinogenicity bioassays. Because the dermal test protocol necessitates dissolving test agents we determined the effects of several solvents on responsiveness of hemizygous mice to dermal applications of the classical skin tumor promoter. phorbol 12-myristate 1...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301317226339
更新日期:2001-09-01 00:00:00
abstract::In tissue slice models, interactions between the heterogeneous cell types comprising the lung parenchyma are maintained thus providing a controlled system for the study of pulmonary toxicology in vitro. However, validation of the model in vitro system must be affirmed. Previous reports, in in vivo systems, have demons...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390183689
更新日期:2003-03-01 00:00:00
abstract::Normal retina and its cell layers are essential for processing visual stimuli, and loss of its integrity has been documented in many disease processes. The numbers and the axonal processes of retinal ganglion cells are reduced substantially in glaucoma, leading to vision loss and blindness. Similarly, selective loss o...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320976375
更新日期:2020-12-31 00:00:00
abstract::The handling-induced dark neuron is a histological artifact observed in brain samples handled before fixation with aldehydes. To explore associations between dark neurons and immunohistochemical alterations in mouse brains, we examined protein products encoded by Cav3 (neuronal perikarya/neurites), Rbbp4 (neuronal nuc...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623319896263
更新日期:2020-04-01 00:00:00
abstract::The 2015 Annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in Minneapolis, Minnesota, at the American College of Veterinary Pathologists/American Society for Veterinary Clinical Pathology/Society of Toxicologic Pathology combined meeting. The goal of this symposium is to p...
journal_title:Toxicologic pathology
pub_type:
doi:10.1177/0192623316631844
更新日期:2016-06-01 00:00:00
abstract::High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT val...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314544379
更新日期:2015-04-01 00:00:00
abstract::Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inocula...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490524247
更新日期:2004-11-01 00:00:00
abstract::Oltipraz, developed as an antischistosomal agent, protects against the hepatotoxicity of many xenobiotics and is known to be an effective inhibitor of experimental carcinogenesis in rodents. In the present study, we investigated its effects on the development of lesions in LEC rats, established as a mutant strain char...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262302753559506
更新日期:2002-03-01 00:00:00
abstract::In carcinogenicity studies with PPAR gamma and alpha/gamma agonists, urinary bladder tumors have been reported in Harlan Sprague-Dawley (HSD) and Charles River Sprague-Dawley (SD) but not Wistar (WI) rats, with urolithiasis purported to be the inciting event. In two 3-month studies, the authors investigated strain-rel...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309332990
更新日期:2009-04-01 00:00:00
abstract::Partial hepatectomy (PH) and neonatal rat short-term liver focus models were used to examine the effects of selected chemicals that had been previously tested in the National Toxicology Program (NTP) 2-yr carcinogenicity studies. C.I. Solvent Yellow 14, monuron, chlorendic acid, and 4-hydroxyacetanilide were tested fo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623389017004110
更新日期:1989-01-01 00:00:00
abstract::Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid fol...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230601047808
更新日期:2006-01-01 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
更新日期:1988-01-01 00:00:00
abstract::To investigate pathogenesis of post-bile duct (BD) injury fibrosis, interlobular BD epithelial injury was induced in male F344 rats by a single IP injection of α-naphthylisothiocyanate (75 mg/kg body weight) and rats were observed for 12 days. On days 1 to 2, cholangiocytes were injured and desquamated. On days 3 to 5...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311413790
更新日期:2011-08-01 00:00:00
abstract::Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety assessment of small molecules, biopharmaceutical agents, and medical devices as an alternate nonrodent species. Although swine have been used extensively in biomedical research, there is a paucity of information in the...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315611762
更新日期:2016-04-01 00:00:00
abstract::A number of factors related to study design have the potential to impact clinical pathology test results during the conduct of nonclinical safety studies. A thorough understanding of these factors is paramount in drawing accurate conclusions from clinical pathology data generated during such studies, particularly when...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623316677066
更新日期:2017-02-01 00:00:00
abstract::In the constantly evolving field of toxicologic pathology, a pathologist's career is often characterized by multiple career transitions. However, these transitions can be challenging and/or overwhelming and may require a shift in focus, strategic approach, and acquisition of new skills and expertise. In order to provi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317736299
更新日期:2017-10-01 00:00:00
abstract::Changes in the mRNA and protein expression of renin-secreting cells in the juxtaglomerular apparatus (JGA) were examined in the rat following administration of ZENECA ZD8731, an angiotensin II receptor antagonist. Doses of 0 or 90 mg/kg were administered daily by gavage for 26 wk. JGA hypertrophy was apparent in histo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339502300303
更新日期:1995-05-01 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::Nedocromil sodium is a nonsteroidal anti-inflammatory drug used to control asthmatic attacks. Our hypothesis is that nedocromil sodium inhibits virus-induced airway inflammation, a common trigger of asthma. We nebulized nedocromil sodium into beagle dogs (n = 10, mean +/- SEM ages: 149 +/- 13 days) before and after in...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800212
更新日期:2000-03-01 00:00:00
abstract::Successful development and use of biomarkers will improve the productivity of oncology drug development. Recognition of the importance of biomarkers for speeding drug development is reflected in the precise definitions and concepts proposed by an NIH Working Group to standardize terminology and promote a more coherent...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230490425021
更新日期:2004-03-01 00:00:00
abstract::This continuing education course presented at the Society of Toxicologic Pathology's 31st Annual Symposium explored and defined the many roles that toxicologic pathologists serve Good Laboratory Practice (GLP)-conducted toxicology and carcinogenicity studies. ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313506521
更新日期:2014-01-01 00:00:00
abstract::Aging is a multifactorial process associated with functional deficits, and the brain is more prone to developing chronic degenerative diseases such as Parkinson's disease. Several groups have tried to correlate the age-related ultrastructural alterations to the neurodegeneration process using in vivo pharmacological m...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318767065
更新日期:2018-04-01 00:00:00
abstract::Results of early nonclinical "General Toxicology" studies are used to set a safe starting dose for first-in-human (FIH) clinical trials. In FIH trials, the research subjects are typically healthy volunteers who have little to gain but much to lose if a trial goes wrong. With that in mind, good laboratory practice regu...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313506878
更新日期:2014-01-01 00:00:00