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 the mammalian genome has provided promising new tools for use in identifying carcinogens and characterizing their (qualitative) risk. Several transgenic mouse lines are currently under study to test their possible use in short-term carcinogenicity testing. One such candidate alternative transgenic model is the XPA knock-out mouse. These mice have an almost complete deficiency in DNA nucleotide excision repair (NER). Nevertheless, XPA-deficient mice are viable and have a background of a low incidence of spontaneous development of cancers. Approximately 15% of the mice develop hepatocellular adenomas (only after 1.5 yr). After treatment with ultraviolet-B radiation or 7,12-dimethylbenz(a)anthracene, the XPA-deficient mice developed squamous cell carcinomas and papillomas, respectively, on their skin. Oral treatment of XPA-deficient mice with benzo[a]pyrene (B[a]P), 2-acetylaminofluorene (2-AAF), and 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) resulted in lymphomas (B[a]P), liver and bladder tumors (2-AAF), and intestinal adenomas plus lymphomas (PhIP). These results look encouraging, but it should be noted that the compounds and agents tested thus far have all been substrate for nucleotide excision repair. Animal studies with different genotoxic or nongenotoxic compounds, as organized for instance within the framework of the International Life Sciences Institute/Health and Environmental Sciences Institute program, are needed to further evaluate the suitability of the XPA model for short-term carcinogenicity testing.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
van Steeg H,Klein H,Beems RB,van Kreijl CFdoi
10.1177/019262339802600605subject
Has Abstractpub_date
1998-11-01 00:00:00pages
742-9issue
6eissn
0192-6233issn
1533-1601journal_volume
26pub_type
杂志文章,评审abstract::Colorectal cancer, responsible for 50,000 deaths per year, is a contributing factor for considerable mortalities in the United States. Consumption of well-done red meat and saturated fats rich in polycyclic aromatic hydrocarbons may be one of the causative factors for sporadic colon cancer. The objective of this study...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309351722
更新日期:2009-12-01 00:00:00
abstract::This report documents the histological changes in nude mouse skin and in human skin xenografts on nude mice following exposure to phenyldichloroarsine (PDA), a vesicant arsenical. Under light microscopy, we observed in PDA-treated human skin grafts: 1) degeneration of epidermal cell nuclei (apparent by 2 hr after expo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500204
更新日期:1987-01-01 00:00:00
abstract::Perfluorooctanoic acid (PFOA) is a chemical used in the production of fluoropolymers. Its persistence in the environment and presence in humans and wildlife has raised health concerns. Liver tumor induction by PFOA is thought to be mediated in rodents by PPAR-alpha. A recent US EPA scientific advisory board questioned...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308318216
更新日期:2008-06-01 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::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::One of the major roles for the toxicologic pathologists now and into the future will be to determine the biologic significance of chemically induced biochemical and molecular alterations detected in whole tissue homogenates or cell cultures. The biologically significant effects will then require further analysis to de...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301301418973
更新日期:2001-01-01 00:00:00
abstract::ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl) phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N-(beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-en...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700203
更新日期:1999-03-01 00:00:00
abstract::The mouse liver is the primary target site for carcinogenesis of more than 200 chemicals (including pesticides, food additives, pharmaceuticals, and industrial intermediates) tested in long-term toxicity safety assessment assays. Mouse liver tumors develop through defined morphological stages (similar to those found i...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339602400117
更新日期:1996-01-01 00:00:00
abstract::The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 we...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339202000206
更新日期:1992-01-01 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
doi:10.1080/01926230701230361
更新日期:2007-04-01 00:00:00
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 ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338301100210
更新日期:1983-01-01 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::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::Kozlowski, C., Brumm, J., and Cain, G. (2018). An Automated Image Analysis Method to Quantify Veterinary Bone Marrow Cellularity on H&E Sections. Tox Path46, 324-335. (Original DOI: 10.1177/0192623318766457). Kozlowski, C., Fullerton, A., Cain, G., Katavolos, P., Bravo, J., and Tarrant, J. M. (2018). Proof of Concept ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,已发布勘误
doi:10.1177/0192623318794946
更新日期:2018-08-01 00:00:00
abstract::Renal tubular hyaline droplets developed in male and female F344 rats bearing a rat fibrosarcoma-derived transplantable tumor (SS). The droplets accumulated exclusively in the proximal renal tubular epithelia as eosinophilic granules of various sizes in hematoxylin and eosin-stained sections. The granules stained brig...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600517
更新日期:1998-09-01 00:00:00
abstract::Mouse renal cell tumors (RCTs) were induced in male CBA mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH)/kg body weight once a week. After a lag period of 2 yr kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glycogen con...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200407
更新日期:1994-07-01 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::S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced nephrotoxicity in vivo was investigated in New Zealand White rabbits. A primary emphasis in these studies was further characterization of DCVC-induced nephrotoxicity using a variety of serum and urinary analytes, including sodium dodecyl sulfate-polyacrylamide gel electr...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339502300405
更新日期:1995-07-01 00:00:00
abstract::A variety of phenotypic cellular changes emerge in the liver of different species prior to the appearance of hepatocellular adenomas and carcinomas induced by carcinogenic agents (chemicals, radiation, hepadna viruses) or develop "spontaneously." Foci of altered hepatocytes have been studied most extensively in rats t...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623389017004107
更新日期:1989-01-01 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
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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 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::Existing liver perfusion models are largely limited by high degrees of ischemic and reperfusion injury and the lack of standardization. To establish a highly standardized perfusion model and minimize reperfusion injury, a porcine liver perfusion model was developed using an artificial heart pump (Buecherl Artificial H...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230590958164
更新日期:2005-01-01 00:00:00
abstract::Pepsinogens are acid protease enzymes of pepsin usually found in gastric mucosa. In the present study, we demonstrated the presence of pepsinogen isozymes in male Syrian golden hamster lung tissues by a combined immunohistochemical and biochemical approach. Immunohistochemically, using rat pepsinogen 1 antibody, pepsi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339101900305
更新日期:1991-01-01 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
abstract::Highly standardized and controlled inhalation studies are required for hazard identification to make test results reproducible and comparable and to fulfill general regulatory requirements for the registration of new drugs, pesticides, or chemicals. Despite significant efforts, the results of inhalation studies have t...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262330002800514
更新日期:2000-09-01 00:00:00
abstract::The Syrian hamster embryo (SHE) cell-transformation assay represents a short-term in vitro assay capable of predicting rodent carcinogenicity of chemicals with a high degree of concordance (LeBoeuf et al [1996]. Mutat Res 356: 85-127). The SHE assay models the earliest identifiable stage in carcinogenicity, morphologi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301753178546
更新日期:2001-01-01 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::Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five, or eight weeks. At five and eight...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308323919
更新日期:2008-10-01 00:00:00
abstract::Female mammals are born with a finite number of ovarian primordial follicles that cannot be regenerated; thus, chemicals that destroy oocytes contained in these follicles can produce premature ovarian failure (early menopuase in women). Exposure of women to known ovotoxicants, such as contaminants in cigarette smoke, ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/019262301301418892
更新日期:2001-01-01 00:00:00