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 by tobacco products. NNK and racemic NNAL are reported to induce lung and pancreatic tumors in rats. The carcinogenicity in Fischer 344 rats of NNK, NNAL, and its enantiomers ( R)-NNAL and ( S)-NNAL has been studied recently, and all test compounds induced significant numbers of lung tumors. We report here the detailed histopathological and immunohistochemical characterization of these tumors and their aggressive nature as shown by their metastasis locally and to the pancreas. The spectrum of treatment-related histopathological findings comprised pulmonary alveolar/bronchiolar (A/B) epithelial hyperplasia, A/B adenomas, and A/B carcinomas. A/B carcinomas frequently exhibited local invasion/metastasis within the mediastinum and thoracic cavity and distant metastasis to the pancreas that was confirmed by immunohistochemistry using the lung-specific markers prosurfactant protein-C and club (Clara) cell-10. Our observation regarding metastasis to the pancreas was an important, and unexpected, finding in this study both for the experimental animal model and potential human relevance.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Kovi RC,Johnson CS,Balbo S,Hecht SS,O'Sullivan MGdoi
10.1177/0192623317751573subject
Has Abstractpub_date
2018-02-01 00:00:00pages
184-192issue
2eissn
0192-6233issn
1533-1601journal_volume
46pub_type
杂志文章abstract::The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500201
更新日期:1987-01-01 00:00:00
abstract::We investigated, morphologically and immunohistochemically, 74 medullary adrenal tumors, including 64 pheochromocytomas (14 malignant and 50 benign), 9 ganglioneuromas, and 1 malignant schwannoma. The tumors were detected in 2-year-old Wistar and Sprague-Dawley rats from carcinogenicity studies. Morphologically, benig...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230290105668
更新日期:2002-07-01 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
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doi:10.1080/01926230601047808
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abstract::Qualitative histopathology has been the gold standard for evaluation of morphological tissue changes in all organ systems, including the peripheral nervous system. However, the human eye is not sensitive enough to detect small changes in quantity or size. Peripheral nervous system toxicity can manifest as subtle chang...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623319854746
更新日期:2020-01-01 00:00:00
abstract::An annular, reddened lesion with mild serosal hemorrhage and no tumorous mass formation was detected in the right uterine horn of a 37-week-old female Sprague-Dawley rat that had postpubertal vaginal bleeding. Histological examination revealed prominent proliferation of the endometrium, which occupied the uterine lume...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313476575
更新日期:2013-01-01 00:00:00
abstract::In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600695474
更新日期:2006-01-01 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::Single doses of aspirin induce scattered foci of necrosis of proximal tubules in some strains of rats, whereas acute or sub-acute administration of phenylbutazone causes renal papillary necrosis. Initially, using Sprague-Dawley rats of CFY and CD strains, it became clear that these rats were not as susceptible to thes...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400214
更新日期:1986-01-01 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::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::A significant correlation exists between average daily food consumption and 2-yr survival in control ad libitum (AL)-fed Sprague-Dawley (SD) rats. SD rats were fed Purina Rodent Chow 5002 or a modified chow, 5002-9, with lower protein, fat, metabolizable energy and increased fiber AL or by dietary restriction (DR) to ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200308
更新日期:1994-05-01 00:00:00
abstract::Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are metabolites of the industrial solvent and environmental contaminant trichloroethylene (TCE), as well as contaminants of chlorinated drinking water. Human exposure to these chemicals is of concern as all three have been shown to increase liver tumor incidence...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339702500501
更新日期:1997-09-01 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::The clinical, laboratory, and pathologic features of a syndrome in dogs characterized by intermittent pain, fever, neutrophilia, and necrotizing arteritis are described to alert others involved in toxicity testing to the existence of this disorder. It is considered that this idiopathic syndrome is a latent condition, ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338901700109
更新日期:1989-01-01 00:00:00
abstract::Laser scanning cytometry (LSC) is a powerful tool for qualitative and quantitative analysis of tissue sections in preclinical drug development. LSC combines the strengths of flow cytometry with tissue architecture retention. This technology has been used predominantly with immunofluorescent techniques on cell culture ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623307312704
更新日期:2008-01-01 00:00:00
abstract::In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrach...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200118
更新日期:1984-01-01 00:00:00
abstract::A factor limiting widespread use of the transgenic rasH2 mouse model for carcinogenicity testing of pharmaceuticals is the paucity of published data on actual drug candidates in rasH2 mice. This report addresses this gap by highlighting rasH2 mouse study data for 10 pharmaceutical candidates. These results were compar...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313477257
更新日期:2013-01-01 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::Chronic prostatitis characterized on light microscopic examination by moderate, multifocal, predominantly lymphocytic inflammation associated with epithelial atypia and intranuclear and cytoplasmic inclusion-like material was identified in the prostate gland of 2 Wistar Han rats administered an immunomodulatory test a...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317713320
更新日期:2017-07-01 00:00:00
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journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230290105811
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journal_title:Toxicologic pathology
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doi:10.1177/0192623320964391
更新日期:2020-12-01 00:00:00
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...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/019262301753178465
更新日期:2001-01-01 00:00:00
abstract::GJA1 gene (Connexin43, also known as Cx43) is the most abundant gap junction protein isoform in animal cells and is associated with bone development in embryos. The objective of the present work was to evaluate in vivo osteal development in GJA1-deficient fetal mice through determination of the histological and molecu...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311422075
更新日期:2011-12-01 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::Animal models have provided an important tool to help make the decision to take potential therapies from preclinical studies to humans. In the past several years, the strong reliance of the pharmaceutical discovery and development process on the use of animal models has come under increasing scrutiny for ethical and s...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314555162
更新日期:2015-01-01 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::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::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::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::Phosphatidylinositol 3-kinases (PI3Ks) regulate intracellular signaling events for multiple cell surface receptors. Phosphatidylinositol 3-kinase δ, 1 of 4 class I PI3K isoforms, is primarily found in leukocytes and regulates immune cell functions. Here, we report changes in the immune and digestive systems that were ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320966238
更新日期:2020-12-01 00:00:00