Altered p53 expression in early stages of chemically induced rodent hepatocarcinogenesis.

Abstract:

:Most available data on the involvement of p53 in rodent carcinogenesis are based on results of the end point of chemically or virally induced carcinogenesis, i.e., tumors. To investigate the role of altered p53 expression in early stages of rodent hepatocarcinogenesis in a systematic way, we treated male Wistar rats for 6 wk, for 13 wk, and for 6 wk followed by a 7-wk recovery period with chemicals classified as genotoxic (200 ppm acetylaminofluorene [AAF], 100 ppm N-nitrosomorpholine [MMN], 200 ppm benzo(a)pyrene), as tumor promoters and carcinogenic in experimental animals (5 ppm ethinylestradiol, 500 ppm phenobarbitone, 3,000 ppm clofibric acid), as carcinogenic in animal experiments (600 ppm thioacetamide), as noncarcinogenic (200 ppm thyroxine), and as tumor promoters in experimental animals (20,000 ppm tryptophan, 120,000 ppm fructose). Immunohistochemical assessment of altered p53 expression on liver sections with polyclonal serum (CM5) resulted in positive staining in 17/21 benzo(a)pyrene-, 1/18 thioacetamide-, 2/21 clofibric acid-, 2/21 phenobarbitone-, 7/19 ethinylestradiol-, 1/21 tryptophan-, 3/19 thyroxine-, and 1/21 fructose-treated rats and in 2/19 controls. These data support earlier results obtained from analogous investigations with a high incidence of altered p53 expression after NNM and AAF treatment. Thus, altered p53 expression appears to be an early and frequent event in rodent carcinogenesis induced by genotoxic chemicals in contrast to most epigenetically acting chemicals.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Wirnitzer U,Töpfer R,Rosenbruch M

doi

10.1177/019262339802600507

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

636-45

issue

5

eissn

0192-6233

issn

1533-1601

journal_volume

26

pub_type

杂志文章
  • Hylan G-F 20 induces delayed foreign body inflammation in Guinea pigs and rabbits.

    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

    authors: Sasaki M,Miyazaki Y,Takahashi T

    更新日期:2003-05-01 00:00:00

  • Sequential morphologic analysis of the nephrotoxicity produced in rats by single doses of chlorozotocin.

    abstract::Chlorozotocin is a chloroethylnitrosourea antitumor agent that is in clinical trial for a variety of human tumors. Renal failure has been a reported side effect of treatment with several of the chloroethylnitrosoureas, including chlorozotocin. To better understand the pathogenesis of this target organ toxicity, we hav...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338601400211

    authors: Dees JH,Kramer RA

    更新日期:1986-01-01 00:00:00

  • Light microscopic sciatic nerve changes in control beagle dogs from toxicity studies.

    abstract::Although the dog is a common choice among nonrodent species in evaluation of compound safety for regulatory submission, information regarding the incidence of spontaneous or incidental microscopic changes in canine peripheral nerve is limited. A retrospective examination was performed of routine histologic preparation...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623311413786

    authors: Whitney KM,Schwartz Sterman AJ,O'Connor J,Foley GL,Garman RH

    更新日期:2011-08-01 00:00:00

  • Urinary tract toxicity in rats following administration of beta 3-adrenoceptor agonists.

    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

    authors: Waghe M,Westwood R,Nunn G,Kalinowski A,Aldridge A

    更新日期:1999-03-01 00:00:00

  • Early alterations of lung injury following acute smoke exposure and 21-aminosteroid treatment.

    abstract::In a simulated fire-related smoke exposure protocol, New Zealand white rabbits were utilized to investigate the potential effects of the 21-aminosteroid (lazaroid) analog U75412E on the early events of acute lung injury. Inhalation of a total of 1.6 mg/kg U75412E aerosolized at a rate of 1.53 mg/min at 0.5 hr after sm...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339902700309

    authors: Wang S,Lantz RC,Robledo RF,Breceda V,Hays AM,Witten ML

    更新日期:1999-05-01 00:00:00

  • Congenital intrahepatic arteriovenous fistulae in a young beagle dog.

    abstract::Congenital intrahepatic arteriovenous fistulae, a rare hepatic vascular anomaly, in an 8-mo-old female beagle dog was investigated. The animal showed anorexia, repeated vomiting, hemorrhagic diarrhea, and jaundice for approximately 2 wk. There was mild to severe increase of serum alkaline phosphatase, glutamic-oxalace...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339702500511

    authors: Yoshizawa K,Oishi Y,Matsumoto M,Fukuhara Y,Makino N,Noto T,Fujii T

    更新日期:1997-09-01 00:00:00

  • The effects of overfeeding and dietary restriction on Sprague-Dawley rat survival and early pathology biomarkers of aging.

    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

    authors: Keenan KP,Smith PF,Hertzog P,Soper K,Ballam GC,Clark RL

    更新日期:1994-05-01 00:00:00

  • The syrian hamster embryo (SHE) cell transformation assay: review of the methods and results.

    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

    authors: Mauthe RJ,Gibson DP,Bunch RT,Custer L

    更新日期:2001-01-01 00:00:00

  • Effects of chronic exposure to air pollution from Sao Paulo city on coronary of Swiss mice, from birth to adulthood.

    abstract::To explore the hypothesis that air pollution promotes cardiovascular changes, Swiss mice were continuously exposed, since birth, in two open-top chambers (filtered and nonfiltered for airborne particles

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623309332994

    authors: Akinaga LM,Lichtenfels AJ,Carvalho-Oliveira R,Caldini EG,Dolhnikoff M,Silva LF,Bueno HM,Pereira LA,Saldiva PH,Garcia ML

    更新日期:2009-04-01 00:00:00

  • Emanuel Edward Klein--the father of British microbiology and the case of the animal vivisection controversy of 1875.

    abstract::The new Appendix A of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, which gives guidelines for accommodation and care of animals and was approved on June 15, 2006, was the main reason the authors decided to investigate the origins of the regulatio...

    journal_title:Toxicologic pathology

    pub_type: 传,历史文章,杂志文章,评审

    doi:10.1177/0192623309345871

    authors: Atalić B,Fatović-Ferencić S

    更新日期:2009-10-01 00:00:00

  • Erratum.

    abstract::Weber, K. (2017). Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats. J Toxicol Pathol45, 64-75. (Original DOI: 10.1177/0192623316672075) In the January 2017 issue of Toxicologic Pathology, a number of in text Table citations were incorrectly labeled. The following are the sentences ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,已发布勘误

    doi:10.1177/0192623317702643

    authors:

    更新日期:2017-04-01 00:00:00

  • Epididymis-specific pathologic disorders in rats exposed to gossypol from weaning through puberty.

    abstract::Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microsc...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230600932455

    authors: de Andrade SF,Oliva SU,Klinefelter GR,De Grava Kempinas W

    更新日期:2006-01-01 00:00:00

  • Flow cytometry in the preclinical development of biopharmaceuticals.

    abstract::Novel biomarkers are often required in the preclinical development of biopharmaceuticals in order to characterize pharmacologic and toxicologic effects and to establish pharmacodynamic and pharmacokinetic relationships. Flow cytometry is uniquely suited for measurement of these biomarkers. Large numbers of single cell...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/019262339902700107

    authors: Gossett KA,Narayanan PK,Williams DM,Gore ER,Herzyk DJ,Hart TK,Sellers TS

    更新日期:1999-01-01 00:00:00

  • Three-dimensional mapping of ozone-induced injury in the nasal airways of monkeys using magnetic resonance imaging and morphometric techniques.

    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

    authors: Carey SA,Minard KR,Trease LL,Wagner JG,Garcia GJ,Ballinger CA,Kimbell JS,Plopper CG,Corley RA,Postlethwait EM,Harkema JR,Einstein DR

    更新日期:2007-01-01 00:00:00

  • Near-optimal conditions for the in vitro culture of hemopoietic progenitor cells in bone marrow from the rat.

    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

    authors: Molyneux G,Rizzo S,Turton J,Phul P,Gibson F

    更新日期:2009-02-01 00:00:00

  • Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute toxicity studies in preclinical trials.

    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

    authors: Fuchs TC,Frick K,Emde B,Czasch S,von Landenberg F,Hewitt P

    更新日期:2012-10-01 00:00:00

  • Complementarity between two rat liver tumor promoters.

    abstract::A delay in the exposure of initiated rats to orotic acid (OA) beyond a specific time frame results in a progressive loss of promotional effect in liver carcinogenesis. The current study was designed to ascertain whether the loss of promotional effect could be counteracted by pre-exposing the initiated animals to other...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338701500212

    authors: Laconi E,Vasudevan S,Rao PM,Rajalakshmi S,Sarma DS

    更新日期:1987-01-01 00:00:00

  • Gastrointestinal damage from nonsteroidal anti-inflammatory drugs.

    abstract::The mechanisms underlying the development of gastrointestinal (GI) damage by the NSAIDs differ considerably from drug to drug. Aside from environmental or intersubject influence (e.g., concurrent disease, physical or sociopsychologic stress, dietary and genetic status), the intrinsic pharmacokinetic and physicochemica...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/019262338801600218

    authors: Rainsford KD

    更新日期:1988-01-01 00:00:00

  • Sequential alteration of apoptosis, p53 expression, and cell proliferation in the rat pancreas treated with 4-hydroxyaminoquinoline 1-oxide.

    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

    authors: Imazawa T,Nishikawa A,Toyoda K,Furukawa F,Mitsui M,Hirose M

    更新日期:2003-11-01 00:00:00

  • Quantitative immunocytochemistry by digital image analysis: application to toxicologic pathology.

    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

    authors: Levine GM,Brousseau P,O'Shaughnessy DJ,Losos GJ

    更新日期:1987-01-01 00:00:00

  • Vascular hamartoma in the uterus of a female Sprague-Dawley rat with an episode of vaginal bleeding.

    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

    authors: Shirota M,Kawashima J,Nakamura T,Ogawa Y,Kamiie J,Shirota K

    更新日期:2013-01-01 00:00:00

  • Potency of carcinogens derived from covalent DNA binding and stimulation of DNA synthesis in rat liver.

    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

    authors: Lutz WK,Büsser MT,Sagelsdorff P

    更新日期:1984-01-01 00:00:00

  • Effects of the antifungal agent itraconazole on proliferative changes of the forestomach mucosa in alloxan-induced diabetic rats.

    abstract::Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623309344204

    authors: Sano T,Ozaki K,Kodama Y,Matsuura T,Narama I

    更新日期:2009-10-01 00:00:00

  • Transplantation of preneoplastic rat hepatocytes by intraportal injection.

    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

    authors: Saeter G,Schwarze PE,Nesland JM,Seglen PO

    更新日期:1987-01-01 00:00:00

  • Significance of sequential cellular changes inside and outside foci of altered hepatocytes during hepatocarcinogenesis.

    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

    authors: Bannasch P,Enzmann H,Klimek F,Weber E,Zerban H

    更新日期:1989-01-01 00:00:00

  • Mammalian Retinal Cell Quantification.

    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

    authors: Muthuswamy A,Chen H,Hu Y,Turner OC,Aina OH

    更新日期:2020-12-31 00:00:00

  • Influence of Study Design Variables on Clinical Pathology Data.

    abstract::A number of factors related to study design have the potential to impact clinical pathology test results during the conduct of nonclinical safety studies. A thorough understanding of these factors is paramount in drawing accurate conclusions from clinical pathology data generated during such studies, particularly when...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/0192623316677066

    authors: Aulbach A,Provencher A,Tripathi N

    更新日期:2017-02-01 00:00:00

  • Applications of laser scanning cytometry in immunohistochemistry and routine histopathology.

    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

    authors: Peterson RA,Krull DL,Butler L

    更新日期:2008-01-01 00:00:00

  • Characterization of Spontaneous Vascular Findings in the Papillary Muscles of Beagle Dogs.

    abstract::Standard histology trimming practices for toxicity studies in dogs include preparation of a section of the papillary muscle associated with the left ventricular free wall-the anteriolateral or anterior muscle. In contrast, the posteromedial or posterior papillary muscle, associated with the interventricular septum, is...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623320963020

    authors: Kohnken R,Weber A

    更新日期:2020-10-01 00:00:00

  • CDER photosafety guidance for industry.

    abstract::In the Federal Register of January 10, 2000 (65 FR 1399), FDA published a draft guidance entitled "Photosafety Testing." The notice gave interested persons an opportunity to submit comments. As a result of the comments, certain sections of the guidance were reworded to improve clarity. A final guidance was published i...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230490463821

    authors: Jacobs AC,Brown PC,Chen C,Ellis A,Farrelly J,Osterberg R

    更新日期:2004-07-01 00:00:00