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 the contribution of PPAR-alpha in PFOA-induced liver tumors. Liver response in CD-1, SV/129 wild-type (WT), and PPAR-alpha knockout (KO) SV/129 mice was evaluated after seven daily treatments of PFOA-NH4(+) (1, 3, or 10 mg/kg, p.o.) or the prototype PPARalpha-agonist Wyeth 14,643 (WY, 50 mg/kg). Livers were examined by light and electron microscopy. Proliferation was quantified after PCNA immunostaining. PFOA treatment induced a dose-dependent increase in hepatocyte hypertrophy and labeling index (LI) similar to WY in WT mice. Ultrastructural alterations of peroxisome proliferation were similar between WY-treated and 10 mg/kg PFOA-treated WT mice. KO mice had a dose-dependent increase in hepatocyte vacuolation but increased LI only at 10 mg PFOA/kg. WY-treated KO mice were not different from KO control. These data suggest that PPAR-alpha is required for WY- and PFOA-induced cellular alterations in WT mouse liver. Hepatic enlargement observed in KO mice may be due to an accumulation of cytoplasmic vacuoles that contain PFOA.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Wolf DC,Moore T,Abbott BD,Rosen MB,Das KP,Zehr RD,Lindstrom AB,Strynar MJ,Lau Cdoi
10.1177/0192623308318216subject
Has Abstractpub_date
2008-06-01 00:00:00pages
632-9issue
4eissn
0192-6233issn
1533-1601pii
0192623308318216journal_volume
36pub_type
杂志文章abstract::Alternate transgenic mouse models are accepted as replacements for the standard carcinogenicity mouse bioassay by regulatory agencies with a companion 2-year rat bioassay. The slower rate of industry acceptance of these shorter transgenic mouse cancer bioassays has been due to lack of historical data and diagnostic cr...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311436181
更新日期:2012-06-01 00:00:00
abstract::Aminoglycoside antibiotics are ototoxic in mammals and birds, including recently hatched chicks, but chicken embryos are insensitive to the ototoxicity of gentamicin, kanamycin, and streptomycin. To determine whether or not the insensitivity is due to a lack of antibiotic distribution to the avian cochlea, the distrib...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200103
更新日期:1994-01-01 00:00:00
abstract::Transgenic mouse strains offer the prospect of significant benefits in the in vivo assessment of carcinogenic potential. The European Regulatory Authorities have been supportive of their inclusion as one of the second-test options in the International Conference on Harmonization of Technical Requirements for the Regis...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230252824879
更新日期:2002-01-01 00:00:00
abstract::Necropsies conducted to support medical device development may be conducted in facilities that do not have the infrastructure in place to support Good Laboratory Practice for Nonclinical Laboratory Studies (GLP) studies and for a variety of reasons they may be conducted without a pathologist present at necropsy. Howev...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315617035
更新日期:2016-01-01 00:00:00
abstract::Toxicology of the male reproductive system has received increased interest in recent years partly fuelled by the growing reports of falling sperm counts and rising reproductive disorders in the human population. Recently revised regulatory guidelines for the safety assessment of pharmaceuticals and chemicals on reprod...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339702500201
更新日期:1997-03-01 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::Carbonyl sulfide (COS) is an odorless gas that produces highly reproducible lesions in the central nervous system. In the present study, the time course for the development of the neurotoxicological lesions was defined and the gene expression changes occurring in the posterior colliculus upon exposure to COS were char...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309335631
更新日期:2009-06-01 00:00:00
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::The dose-response of diethylnitrosamine (DENA) initiation of hepatocarcinogenesis was determined in infant Balb/c male mice with and without subsequent phenobarbital treatment. Male Balb/c mice received a single intraperitoneal injection of DENA (0, 2.5, 10.0, 25.0 or 50.0 micrograms/gbw) in saline on day 15 of age. N...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338801600310
更新日期:1988-01-01 00:00:00
abstract::Focal spontaneously occurring eosinophilic hypertrophic cells, histomorphologically resembling oncocytes and hepatocytes, were observed in the pancreas from 11 (0.3%) of 4,177 Sprague-Dawley rats, 3 to 26 months old. The age of these eleven rats ranged from 13 to 25 months. The incidence was not different between sexe...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500101
更新日期:1987-01-01 00:00:00
abstract::Systemic hypoxemia, occurring in space-occupying lung pathologies such as inflammation and neoplasms. reduces the gas exchange area and stimulates catecholamine secretion from the adrenal medulla where chronic endocrine hyperactivity may lead to hyperplasia and neoplasia. We investigated the possible correlation betwe...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262302753559605
更新日期:2002-03-01 00:00:00
abstract::The spleen contains hematopoietic and lymphoid elements, is a primary site of extramedullary hematopoiesis, and removes degenerate and aged red blood cells as well as particulate materials and circulating bacteria from the blood supply. Lesions of this important component of the immune system may center on the red pul...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600867750
更新日期:2006-01-01 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::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 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::Pineal gland tumors are very rare brain lesions in rats as well as in other species including humans. A total of 8 (out of 1,360 examined) Wistar rats from 3 different combined chronic toxicity/carcinogenicity or mere carcinogenicity studies revealed pineal gland tumors. The tumors were regarded to be spontaneous and ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315572700
更新日期:2015-08-01 00:00:00
abstract::The chloracetanilide herbicide alachlor (2-chloro-2',6-diethyl-N-(methoxymethyl)-acetanilide) induces nasal neoplasms in rats following chronic dietary exposure. The present study sought to identify the cellular origin and mechanisms of tumor induction and progression. Male Long-Evans rats were fed alachlor (0 or 126 ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800602
更新日期:2000-11-01 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::We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine t...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623314532036
更新日期:2015-02-01 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::This experiment evaluated effects following chronic toxicity with 20 ppm fenvalerate (synthetic pyrethroid), 2 ppm monocrotophos (organophosphate) and 2 ppm endosulfan (chlorinated hydrocarbon) on bone health of broiler chicks. A total of 120 chicks were divided equally into 4 groups and were fed poultry mash without ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490431745
更新日期:2004-05-01 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::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::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::Exposure to synthetic fibers with employment in textile mills can be associated with an elevated risk of interstitial lung disease (ILD). A mechanism of injury has not been determined. ILD can follow exposures to inorganic fibers (e.g., asbestos) which are associated with a mobilization of iron and catalysis of an oxi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932448
更新日期:2006-01-01 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::The target organ specificities of cell proliferation and histopathological lesion induction by 5 carcinogens having different target organs were evaluated using a multiorgan carcinogenesis bioassay. In Group 1, male F-344 rats aged 6 wk were sequentially treated with N-diethylnitrosamine (DEN, single 100-mg/kg ip inje...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100502
更新日期:1993-09-01 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
pub_type: 杂志文章
doi:10.1177/0192623320969124
更新日期:2020-12-21 00:00:00
abstract::The evaluation of neurotoxic damage involves a unique set of challenges. Vulnerable structures, such as neocortex, hippocampus, spinal cord, and peripheral nerve are complex and sharply differentiated; deficits can result from insults to one or more element(s) in the system (e.g., myelin, axon, soma, synapse, or glia)...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623310390231
更新日期:2011-01-01 00:00:00
abstract::The toxicity of polybrominated diphenyl ethers (PBDEs), flame-retardant components, was characterized in offspring from Wistar Han dams exposed by gavage to a PBDE mixture (DE71) starting at gestation day 6 and continuing to weaning on postnatal day (PND) 21. Offspring from the dams underwent PBDE direct dosing by gav...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311429973
更新日期:2012-01-01 00:00:00