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 confirmations in animals of the carcinogenicity of many antitumor agents. Furthermore, these agents have been associated with human tumors in numerous case reports. Review of the literature also indicates the inability of animal studies to predict the sites of carcinogen-induced tumors in man. The carcinogenic risk assessment of antitumor agents should begin with the determination of the ability of the agent to interact with DNA. Those agents which are capable of alkylating or binding DNA should be tested for mutagenic and teratogenic potential. The presumption of carcinogenicity should be made for DNA-reactive, mutagenic/teratogenic antitumor agents without requiring confirmation in long-term carcinogenicity bioassays in large numbers of animals. The inability of carcinogenicity studies in animals to accurately predict potential human tumor sites must also be recognized.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Hottendorf GHdoi
10.1177/019262338501300305subject
Has Abstractpub_date
1985-01-01 00:00:00pages
192-9issue
3eissn
0192-6233issn
1533-1601journal_volume
13pub_type
杂志文章abstract::Recent clinical evidence suggests that hylan, a modified hyaluronan, and related products potentially elicit foreign body granulomatous inflammation in human soft tissue. We investigated the biocompatibility of hylan G-F 20 (Synvisc) for up to 28 days after intradermal injection in guinea pigs and intramuscular inject...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390204360
更新日期:2003-05-01 00:00:00
abstract::Microminipigs have become an attractive animal model for toxicology and pharmacology studies and for human disease models, owing to their manageable size. Although there are numerous reports of spontaneous age-related lesions in mice, rats, dogs, and monkeys, those in minipigs are scarce. In the present study, spontan...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623319861350
更新日期:2019-10-01 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::Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314526006
更新日期:2014-06-01 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::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::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::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::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::(+/-)-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol) and 9-hydroxybenzo(a)pyrene (9-OH-BP) were metabolized by rat liver microsomes in the presence of calf thymus DNA, resulting in preferential DNA binding of fluorescent (+)-anti-BP-7,8-diol-9,10-epoxide (BPDE) and 9-OH-BP-4,5-epoxide, respectively. When the ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200211
更新日期:1984-01-01 00:00:00
abstract::Furan is a potent cholangiocarcinogen in rat by an as yet undefined mechanism. The risk to man remains unclear. Using a time-course stop study design, we have investigated the potential of furan to induce oxidative stress and DNA damage associated with inflammatory and regenerative responses in rat liver. Furan was ad...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309357946
更新日期:2010-02-01 00:00:00
abstract::Changes in p53 expression, apoptosis and cell proliferation after treatment with 4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and liver, target and nontarget organs for tumorigenesis, respectively. Male rats were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390241855
更新日期:2003-11-01 00:00:00
abstract::Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists are used in the treatment of type 2 diabetes mellitus and hyperlipidemias. In carcinogenicity studies, some of these agonists induced hemangiomas/hemangiosarcomas in mice, but not in rats. We hypothesized that increased endothe...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311422080
更新日期:2011-12-01 00:00:00
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::We describe 2 cases of a relatively rare tumor diagnosed as pituicytoma in the pars nervosa of rat pituitary. This tumor was spontaneously noted in one 110-week-old female and one 109-week-old male Fischer 344 (F344)/DuCrj rats during 2-year carcinogenicity studies. Although no gross abnormality of the pituitary was d...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800612
更新日期:2000-11-01 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::The lung is a target organ for the toxic effects of several chemical agents, including natural products, industrial chemicals, pesticides, environmental agents, and occasionally, drugs. Factors that establish the lung as a target organ include selective tissue exposure, high tissue oxygenation, and the presence of bio...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339101900415
更新日期:1991-01-01 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::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 spontaneous multicystic peritoneal mesothelioma was detected in a 108-wk-old male Fischer-344/DuCrj rat. Grossly, a tumor containing numerous, semi-transparent, variously sized, thin-walled cysts was found on the splenic serosal surface. Microscopically, each cyst was surrounded by variable amounts of loose connecti...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100111
更新日期:1993-01-01 00:00:00
abstract::A rat liver foci bioassay (RLFB) based on an initiation-promotion protocol employing preneoplastic foci of altered hepatocytes (FAH) as an endpoint, was prevalidated in 5 different laboratories. FAH were identified by immunohistochemical demonstration of glutathione-S-transferase (placental form, GSTP) and by staining...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390173888
更新日期:2003-01-01 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::Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are well recognized as a major class of therapeutic agent that causes renal papillary necrosis (RPN). Over the last decade a broad spectrum of other therapeutic agents and many chemicals have also been reported that have the potential to cause this lesion in...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339802600110
更新日期:1998-01-01 00:00:00
abstract::Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentratio...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309340277
更新日期:2009-08-01 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::Sprague-Dawley CD rats received daily oral doses (45 mg/kg) of the cationic amphiphilic tricyclic antidepressant imipramine HCl (Tofranil) for up to two years. Representative specimens of liver, lung, spleen, mesenteric lymph node, retina and dorsal root ganglion were examined for myeloid bodies (MB). The extent that ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338301100102
更新日期:1983-01-01 00:00:00
abstract::Zibotentan, an endothelin-A receptor antagonist, has been used in the treatment of various cardiovascular disorders and neoplasia. Castrated athymic nude mice receiving zibotentan for a preclinical xenograft efficacy study experienced weight loss, gastrointestinal bloat, and the presence of an audible respiratory clic...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318816295
更新日期:2019-02-01 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::We have developed a guinea pig model of iron overload toxicity. Animals were administered intraperitoneal iron dextran 3 times a week to achieve total body iron load of 0.25, 0.5, 1.0, 1.5, and 2.0 g Fe/kg body weight in less than 30 days. Quantitation of tissue iron levels with atomic absorption indicated increased i...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100307
更新日期:1993-01-01 00:00:00
abstract::Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epith...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339202000311
更新日期:1992-01-01 00:00:00