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 content, basophilia, and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and gamma-glutamyltranspeptidase (GGT). RCTs displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with the normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK, LDH) and the pentose phosphate pathway (G6PDH), while negative G6Pase and low SDH activity were observed in these cells. The majority of RCTs showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCTs. Markedly enlarged cells with atypical nuclei were detected in some advanced RCTs. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in these enlarged cells than in other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in RCTs in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early during carcinogenesis, but additional studies on early stages of renal carcinogenesis are needed to substantiate this assumption.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Ahn YS,Chemeris GY,Turusov VS,Bannasch Pdoi
10.1177/019262339402200407subject
Has Abstractpub_date
1994-07-01 00:00:00pages
415-22issue
4eissn
0192-6233issn
1533-1601journal_volume
22pub_type
杂志文章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
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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
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doi:10.1177/019262339402200103
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abstract::Two-year mouse and rat bioassay studies of 2-methylimidazole (2-MI) conducted by the National Toxicology Program revealed that epididymal sperm granuloma(SG)s occurred only in male B6C3F1 mice in a dose-related manner. The present study characterized 2-MI-induced SGs in these epididymides. Groups of 50 male B6C3F1 mic...
journal_title:Toxicologic pathology
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doi:10.1080/01926230590922866
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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
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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
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abstract::Transgenic Tg.AC mice carry a v-Ha-ras coding region flanked by a zeta-globin promoter and an SV40 polyadenylation signal sequence. These mice respond to carcinogens by developing epidermal papillomas. In some cases, malignancies develop at the sites of these papillomas. Various patterns of squamous cell differentiati...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600407
更新日期:1998-07-01 00:00:00
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
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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
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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
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abstract::The effects of oral contraceptives have been studied in the beagle bitch for periods up to 7 yr. High doses of these potent estrogen: progestogen (E:P) combinations have been shown to promote tumors in the mammary glands, smooth muscle of the tubular genitalia, and occasionally in the transitional epithelium of the ne...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
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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
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更新日期:2013-01-01 00:00:00
abstract::The toxic effects of a mixture of 2-aminoanthracene (2-AA), benzanthracene (BA), and dinitropyrene isomers (DNP), and the toxic effects of these compounds individually, were investigated in the Fischer-344 rat following dietary exposure via a powdered basal diet. Animals were sacrificed at 14-, 30-, and 80-days of die...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301316905291
更新日期:2001-05-01 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
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更新日期:1986-01-01 00:00:00
abstract::After 15 years of existence, the ACVP/STP Coalition for Veterinary Pathology Fellows will dissolve, primarily due to lack of renewed financial sponsorship. While in operation, the Coalition organized 32 new training position for veterinary pathologists, supported by $7.4 M from sponsors, including pharmaceutical and b...
journal_title:Toxicologic pathology
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doi:10.1177/0192623320917970
更新日期:2020-06-01 00:00:00
abstract::Cancer affects approximately 1 in 3 individuals. An individual's susceptibility to cancer is partly determined by environmental exposures and by the combination of inherited cancer susceptibility and resistance genes. Initial mapping of these low penetrance cancer susceptibility genes has been done in the mouse becaus...
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更新日期:2004-03-01 00:00:00
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journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339001800106
更新日期:1990-01-01 00:00:00
abstract::Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis, secretion, and metabolism of thyroid hormones. This includes (a) inhibition of the iodine trapping mechanism, (b) blockage of or...
journal_title:Toxicologic pathology
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更新日期:1997-01-01 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
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更新日期:1987-01-01 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
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journal_title:Toxicologic pathology
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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
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更新日期:1997-07-01 00:00:00
abstract::BMS-645737, an inhibitor of vascular endothelial growth factor (VEGF) receptor-2 and fibroblast growth factor (FGF) receptor-1, has anti-angiogenic activity and was evaluated in nonclinical studies as a treatment for cancer. This article characterizes the BMS-645737-induced clinical, gross, and histologic lesions of i...
journal_title:Toxicologic pathology
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abstract::Cells have to double their protein mass in order to divide. Whether this is achieved through increased synthesis (PS), decreased degradation (PD), or a combination of both is still debated. Likewise open are other basic questions: whether, beyond differences relating to growth phase (GP) or rate, reduced PD rates are ...
journal_title:Toxicologic pathology
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abstract::More than 40% of compounds identified through combinatorial screening programs are poorly soluble in water. These molecules are difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues. Formulating these compounds as pure drug nanoparticles is one ...
journal_title:Toxicologic pathology
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更新日期:2008-01-01 00:00:00
abstract::Changes in the mRNA and protein expression of renin-secreting cells in the juxtaglomerular apparatus (JGA) were examined in the rat following administration of ZENECA ZD8731, an angiotensin II receptor antagonist. Doses of 0 or 90 mg/kg were administered daily by gavage for 26 wk. JGA hypertrophy was apparent in histo...
journal_title:Toxicologic pathology
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更新日期:1995-05-01 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
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abstract::Complete evaluation of the toxicity of a new chemical entity requires critical analysis of the pattern of positive and negative findings in all types of toxicity tests, pharmacokinetics and metabolism in the species examined, and correlation of the effects with information about its pharmacodynamic and pharmacological...
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更新日期:1994-03-01 00:00:00