Abstract:
:The performance of the p53-/- transgenic (knockout) mouse model was evaluated through review of the data from 31 short-term carcinogenicity studies with 21 compounds tested as part of the International Life Sciences Institute's (ILSI) Alternatives to Carcinogenicity Testing (ACT) project, together with data from other studies which used comparable protocols. As expected based on the hypothesis for the model, a significant number (12/16 or 75%) of the genotoxic human and/or rodent carcinogens tested were positive and the positive control, p-cresidine, gave reproducible responses across laboratories (18/19 studies positive in bladder). An immunosuppressive human carcinogen, cyclosporin A, was positive for lymphomas but produced a similar response in wild type mice. Two hormones that are human tumorigens, diethylstilbestrol and 17beta-estradiol, gave positive and equivocal results, respectively, in the pituitary with p53-deficient mice showing a greater incidence of proliferative lesions than wild type. None of the 22 nongenotoxic rodent carcinogens that have been tested produced a positive response but 2 compounds in this category, chloroform and diethylhexylphthalate, were judged equivocal based on effects in liver and kidney respectively. Four genotoxic noncarcinogens and 6 nongenotoxic, noncarcinogens were also negative. In total (excluding compounds with equivocal results), 42 of 48 compounds or 88% gave results that were concordant with expectations. The technical lessons learned from the ILSI ACT-sponsored testing in the p53+/- model are discussed.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Storer RD,French JE,Haseman J,Hajian G,LeGrand EK,Long GG,Mixson LA,Ochoa R,Sagartz JE,Soper KAdoi
10.1080/019262301753178465subject
Has Abstractpub_date
2001-01-01 00:00:00pages
30-50eissn
0192-6233issn
1533-1601journal_volume
29 Supplpub_type
杂志文章,评审abstract::Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug exposure in animals and for ensuring that drug exposure is substantially greater in animals than that expected in humans at therapeutic doses. The usefulness of TK studies can be further enhanced by correlating TK parameters with relevant tox...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339502300209
更新日期:1995-03-01 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::When chemicals that are nongenotoxic in conventional assays produce increases in tumor incidence in rodents in chronic bioassays, the determination of the significance of these data for human safety is a challenging task. An important first step in this process is consideration of available data on the mechanism of ac...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339402200206
更新日期:1994-03-01 00:00:00
abstract::2,3-Pentanedione (PD) is a component of artificial butter flavorings. The use of PD is increasing since diacetyl, a major butter flavorant, was associated with bronchiolitis obliterans (BO) in workers and has been removed from many products. Because the toxicity of inhaled PD is unknown, these studies were conducted t...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311431946
更新日期:2012-04-01 00:00:00
abstract::Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis, secretion, and metabolism of thyroid hormones. This includes (a) inhibition of the iodine trapping mechanism, (b) blockage of or...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339702500109
更新日期:1997-01-01 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::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::At present (putative) human carcinogens are identified via epidemiological studies and testing using the chronic 2-yr rodent bioassay. Both methods have severe limitations in that they are slow, insensitive, expensive, and are also hampered by many uncertainties. The development of methods to modify specific genes in ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339802600605
更新日期:1998-11-01 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::With the increasing use of animal-based biomaterials for regenerative medical applications, the need for their safety assessment is paramount. A porcine cholecyst-derived scaffold (CDS), intended as a muscle repair graft, prepared by a nondetergent/enzymatic method was engrafted in a rat abdominal wall defect model. H...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317752894
更新日期:2018-02-01 00:00:00
abstract::Age-related changes in gross and microscopic structure of the nasal cavity may alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techn...
journal_title:Toxicologic pathology
pub_type: 杂志文章,多中心研究
doi:10.1080/01926230601072343
更新日期:2007-01-01 00:00:00
abstract::A semiautomated quantitative assay for rat serum alkaline phosphatase (ALP) isoenzyme determination was developed, incorporating selective precipitation of bone alkaline phosphatase (BALP) with wheat germ lectin and differential inhibition with levamisole for determination of intestinal alkaline phosphatase (IALP). Th...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200607
更新日期:1994-11-01 00:00:00
abstract::The administration of mesenchymal stromal cells (MSCs) provides an exciting emerging therapeutic modality for the treatment of peripheral arterial disease, a condition that is associated with critical limb ischemia as its end stage. Placental-derived MSCs, termed PLX-PAD cells, are stable adhesive stromal cells isolat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309338383
更新日期:2009-08-01 00:00:00
abstract::Nephrotoxic renal injury, and especially drug nephrotoxicity is now a common cause of acute renal failure. The most common patterns of renal injury produced by nephrotoxins, tubular damage, and interstitial nephritis, are discussed here. Toxic agents which are primarily tubular toxins include certain antibiotics, cisp...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400106
更新日期:1986-01-01 00:00:00
abstract::This report describes the findings of preclinical testing of SCH 351591, a selective phosphodiesterase 4 inhibitor, in CD-1 mice over a wide range of doses, in which the heart and reproductive organs of both sexes demonstrated toxic effects. Repeat-dose toxicity studies assessed 5, 15, 50, 100, 200, 400, and 800 mg/kg...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310370463
更新日期:2010-06-01 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::Hepatocyte suspensions prepared from inbred male Wistar-Kyoto rats were transplanted to the livers of syngeneic recipients by injection into the portal venous system immediately after partial hepatectomy. Donor cells were labelled with 51Cr in vitro before transplantation. Animals were sacrificed 1 hr, 10 hr, 48 hr, o...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500110
更新日期:1987-01-01 00:00:00
abstract::Bioabsorbable implants can be advantageous for certain surgical tissue bioengineering applications and implant-assisted tissue repair. They offer the obvious benefits of nonpermanence and eventual restoration of the native tissue's biomechanical and immunological properties, while providing a structural scaffold for h...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623318816681
更新日期:2019-04-01 00:00:00
abstract::To characterize the promoting activity of thiobenzamide (TB), a thiono-sulfur-containing xenobiotic, rats of both sexes were treated with the compound for 4 or 8 weeks after an initiating dose of diethyl-nitrosamine. The number, area (volume), and phenotypic complexity of the enzyme-altered hepatocyte foci were studie...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400314
更新日期:1986-01-01 00:00:00
abstract::Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SH...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623312441405
更新日期:2012-07-01 00:00:00
abstract::A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We used two multiplex assays for these novel biomarkers to quantify biomarker concentration in serial urine collections from rats of both sexes administered varying concentrations of cisplatin...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311432436
更新日期:2012-04-01 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::Toxic injury occurs in the liver more often than any other organ. This can be attributed to the fact that virtually all ingested substances that are absorbed are first presented to the liver and that the liver is responsible for the metabolism and elimination of many substances. Drug-induced liver injury has become a ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230590522428
更新日期:2005-01-01 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::Monocrotaline pyrrole (MCTP) is a highly reactive pneumotoxic metabolite of the pyrrolizidine alkaloid plant toxin monocrotaline. When administered to rats, it causes a delayed and progressive lung injury, vascular remodeling, and pulmonary hypertension. Structural remodeling consists of endothelial cell swelling foll...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339702500405
更新日期:1997-07-01 00:00:00
abstract::I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium "Toxicologic Pathology and the Immune System." I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my r...
journal_title:Toxicologic pathology
pub_type: 历史文章
doi:10.1177/0192623311427710
更新日期:2012-01-01 00:00:00
abstract::There is increased interest to use minipigs in ocular toxicology studies due to their anatomical similarities with human eyes and as a substitute for nonhuman primates. This requires adaptation of enhanced optical coherence tomography (OCT) techniques and of ocular relevant immunohistochemistry (IHC) or in situ hybrid...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315615553
更新日期:2016-04-01 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::The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak that started in Wuhan, China, in 2019 resulted in a pandemic not seen for a century, and there is an urgent need to develop safe and efficacious vaccines. The scientific community has made tremendous efforts to understand the disease, and unpara...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623320959090
更新日期:2020-10-01 00:00:00
abstract::Tubular injury sensitizes glomeruli to injury. We review potential mechanisms of this tubuloglomerular cross talk. In the same nephron, tubular injury can cause stenosis of the glomerulotubular junction and finally result in atubular glomeruli. Tubular injury also affects glomerular filtration function through tubulog...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623318796784
更新日期:2018-12-01 00:00:00