Abstract:
:Benzo[a]pyrene (BP) is mutagenic but noncarcinogenic in the murine colon. Recently, we reported rapid induction of colonic tumors by treatment of CD2F1 mice with BP (125 mg/kg for 5 days) followed by a colitis inducer, dextran sulfate sodium (DSS) (4% in drinking water for 1 or 2 weeks). However, there are no reports on detailed time course and histopathological features of colonic proliferative lesions in this model. Here, we show the detailed time course of colonic dysplasia, adenoma and adenocarcinoma induced by treatment with BP, DSS, and a combination of the two (BP/DSS). In the colon of mice exposed to BP/DSS, 14.6 dysplastic foci per mouse were present one week after DSS treatment (week 4). The number of dysplastic foci decreased with time to 3.1 at week 9 and thereafter remained almost constant. At week 4, 1.5 adenocarcinomas were also observed, with a marked increase in numbers with time, reaching 29.3 at week 14. In contrast, the number of dysplastic foci induced by DSS alone showed a time course similar to that following BP/DSS treatment; however, only a few tumors appeared. Neither dysplastic foci nor neoplastic lesions were induced by BP only. In mice exposed to BP/DSS, β-catenin was demonstrated immunohistochemically in the nucleus and/or cytoplasm of the tumor cells, and this translocation from the cell membrane was evident in subsets of dysplastic foci. In dysplastic foci induced by DSS alone, β-catenin was absent in the nucleus/cytoplasm. These finding suggest that aberrant β-catenin accumulation in dysplastic foci is associated with tumor progression in this BP/DSS model.
journal_name
J Toxicol Patholjournal_title
Journal of toxicologic pathologyauthors
Sonoda J,Seki Y,Hakura A,Hosokawa Sdoi
10.1293/tox.2014-0061subject
Has Abstractpub_date
2015-04-01 00:00:00pages
109-20issue
2eissn
0914-9198issn
1881-915Xpii
2014-0061journal_volume
28pub_type
杂志文章abstract::We investigated chronological changes in immunohistochemical phenotyping in the thymus and spleen in Crl:CD rats up to the age of about one year. In the thymus, T cells increased markedly from 3 to 4 weeks of age. Proliferating cells also increased markedly at these points. B cells tended towards an increase with age....
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.25.55
更新日期:2012-03-01 00:00:00
abstract::The aim of this work was to investigate the potential interactions between intestinal absorbance and ricin poisoning. The Caco-2 cell monolayer and everted intestinal sac (VEIS) models were used. The distribution of ricin in CD-1 mice intoxicated with 0.1 mg/kg of ricin intragastrically was determined by immunohistoch...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2013-0049
更新日期:2014-04-01 00:00:00
abstract::A guinea pig (9-week-old) that had been placed in a control group for a pharmacological test was found to have a single nodule on the surface of the right ventricular wall. In a transverse section of the heart after fixation, a whitish mass was found that extended from the subendocardium to the subepicardium of the ri...
journal_title:Journal of toxicologic pathology
pub_type:
doi:10.1293/tox.23.107
更新日期:2010-06-01 00:00:00
abstract::Tumor research has largely relied on xenograft models created by the engraftment of cultured cell lines derived from tumor tissues into immunodeficient mice for in vivo studies. Like in vitro models, such models retain the ability of tumor cells to continuously proliferate, so they have been used to predict the clinic...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1293/tox.2020-0007
更新日期:2020-07-01 00:00:00
abstract::Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristic...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2016-0035
更新日期:2017-01-01 00:00:00
abstract::Brain changes associated with risperidone, a dopamine-2/serotonin-2 receptor antagonist, have been documented in rats and humans, but not in nonhuman primates. This study characterized brain changes associated with risperidone in nonhuman primates. Rhesus monkeys were orally administered risperidone in a dose-escalati...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2019-0004
更新日期:2019-10-01 00:00:00
abstract::To clarify the modifying effect of N-Acetyl-L-Cysteine (NAC), which has antioxidative ability, on hepatocarcinogenesis promoted by fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR) alpha agonist , male F344/N rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) as...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.22.255
更新日期:2009-12-01 00:00:00
abstract::Accurate analysis of female reproductive toxicity requires a thorough understanding the differences in and specifics of estrous or menstrual cycles between laboratory animals. There are some species differences such as the time of sex maturation, the length of the estrous or menstrual cycle, the length of the luteal p...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1293/tox.2016-0021
更新日期:2016-07-01 00:00:00
abstract::Diabetes mellitus (DM) and obesity are believed to be risk factors for colorectal cancer in humans. In experiment 1, male nondiabetic Long-Evans Tokushima Otsuka (LETO) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model animal of type 2 DM, were whole-body X-irradiated (4 Gy) at 6 and 8 weeks of age and ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.24.187
更新日期:2011-12-01 00:00:00
abstract::Liposomes have been used as a vehicle for encapsulating chemicals or toxins in toxicological studies. We investigated the transient effects of empty liposomes on hepatic macrophages by applying a single intravenous injection at a dose of 10 ml/kg body weight in 6-week-old male F344 rats. One day after injection, the n...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2015-0082
更新日期:2016-04-01 00:00:00
abstract::The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative among the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internatio...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1293/tox.31.1S
更新日期:2018-01-01 00:00:00
abstract::Chronic lung injury resulting from a variety of different causes is frequently associated with the develop ment of pulmonary fibrosis in humans. Although the etiology of pulmonary fibrosis is generally unknown, several sources of evidence support the hypothesis that a number of environmental and occupational agents pl...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.24.9
更新日期:2011-03-01 00:00:00
abstract::Endogenous prostaglandin (PG) E(2) plays important roles in renal homeostasis. Immunoexpressions of PGE(2) biosynthesis-related enzymes, cyclooxygenase (COX)-2 and microsomal PGE(2) synthetase (mPGES)-1 and EP4 (a PGE(2) receptor), were investigated in renal development. Kidney tissues were obtained from fetuses on ge...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.24.257
更新日期:2011-12-01 00:00:00
abstract::Numerous pieces of evidence have revealed that oxaliplatin (OXA) evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome side effects needs to be further investigated. It is well known that cyclooxygenase-2 (COX-2) and extracellular signal-regulated kinases (ERK1/2) signaling pl...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2016-0032
更新日期:2016-10-01 00:00:00
abstract::Intratracheal instillation is the introduction of a substance directly into the trachea. Intratracheal instillation has been used to investigate the lung toxicity of several chemicals and requires the suspension or dissolution of test material in a vehicle for even dispersal throughout the lung. Importantly, the toxic...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2019-0060
更新日期:2020-01-01 00:00:00
abstract::It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the e...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2018-0009
更新日期:2018-10-01 00:00:00
abstract::The antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) have been used for treatment of hyperthyroidism for more than several decades, despite the fact that they are associated with adverse drug reactions that are thought to be autoimmune mediated. We therefore examined histopathologic responses in t...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2013-0012
更新日期:2013-12-01 00:00:00
abstract::The involvement of the lung during the septic systemic inflammatory response elicited by administration of lipopolysaccharide (LPS) was investigated. Eight-week-old male Sprague-Dawley rats were injected i.p. with 15 mg/kg LPS. After 24 h, the lungs were excised to evaluate the cellular responses to LPS. Matrix-assist...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2014-0053
更新日期:2015-01-01 00:00:00
abstract::Busulfan, an antineoplastic bifunctional-alkylating agent, is known to induce developmental anomalies. In the present study, we examined the distribution and sequence of pyknotic cells in rat fetal tissues exposed to busulfan. Pregnant rats on gestation day 13 were administered intraperitoneally 30 mg/kg of busulfan, ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.22.167
更新日期:2009-09-01 00:00:00
abstract::This study aimed to establish a rat chronic kidney disease (CKD) model by studying the effects of a high-phosphorus diet in rats that had undergone partial ligation of the renal arteries (RL). Separate groups of 10-week-old male Slc:Sprague-Dawley rats underwent RL and were fed diets with varying phosphorous levels fo...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2019-0086
更新日期:2020-04-01 00:00:00
abstract::Cigarette smoking is one of the major risk factors of bladder cancer in humans. To date, however, there is no experimental evidence for the effects of inhalation exposure to mainstream cigarette smoke on bladder carcinogenesis. The purpose of the present study was to evaluate the effect of inhalation of mainstream cig...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2013-0039
更新日期:2013-12-01 00:00:00
abstract::The term cardiomyopathy is used to describe heart disease resulting from an abnormality in the myocardium. It is rare in cynomolgus macaques (Macaca fascicularis). Here, we report a case of hypertrophic cardiomyopathy in an 11-year-old male cynomolgus macaque. Macroscopically, the interventricular septum (IVS) and the...
journal_title:Journal of toxicologic pathology
pub_type:
doi:10.1293/tox.2017-0027
更新日期:2018-01-01 00:00:00
abstract::Endometrial adenocarcinoma in the uterine corpus is a malignant cancer that occurs in menopausal women and aged rodents. Because of the similarities in pathogenesis and morphology of endometrial adenocarcinoma in rodents and humans, prediction of the modes of action (MOA) in uterine carcinogenesis is important for ext...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2015-0026
更新日期:2015-10-01 00:00:00
abstract::We performed a medaka bioassay for the carcinogenicity of methylazoxymethaol acetate (MAM-Ac) to examine the sequential histological changes in the liver from 3 days after exposure until tumor development. The medaka were exposed to MAM-Ac at a concentration of 2 ppm for 24 hours, and were necropsied at 3, 7, 10, 14, ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2020-0033
更新日期:2020-10-01 00:00:00
abstract::A single mass was found on the left submandibular salivary gland at necropsy of a 15-month-old male commercially bred laboratory Beagle dog from a control dose group from a repeat toxicity study. Microscopically, the mass was composed of a well-demarcated area of coagulative necrosis surrounded and separated from the ...
journal_title:Journal of toxicologic pathology
pub_type:
doi:10.1293/tox.2015-0018
更新日期:2015-07-01 00:00:00
abstract::The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.23.171
更新日期:2010-09-01 00:00:00
abstract::Uterine deciduomas were found in two female virgin rats, a 15-week-old Lewis rat and a 7-week-old Sprague-Dawley rat. The firm white nodules were located at the base of unilateral uterine horns and were approximately 6 mm and 4 mm in diameter. Histopathologically, the nodules were composed of three areas, each with a ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.26.61
更新日期:2013-03-01 00:00:00
abstract::Sarcopenia is the age-related decrease of muscle mass and function. Diabetes and obesity are known to be risk factors that exacerbate sarcopenia, but the underlying mechanism of diabetes-related sarcopenia is still unknown. Obese type 2 diabetes SDT fatty rats show early onset of severe diabetes and there have been no...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2017-0064
更新日期:2018-04-01 00:00:00
abstract::To prevent fixation defects or artifacts in the whole bodies of fish caused by conventional fixatives, such as formalin solution, Bouin's fluid (BF), and Davidson's fluid (DF), the optimal fixatives and fixing method were examined. An improved method of fixing the whole bodies of fish was examined that makes use of a ...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.2018-0001
更新日期:2018-07-01 00:00:00
abstract::Dysferlin (DYSF) is involved in the membrane-repair process, in the intracellular vesicle system and in T-tubule development in skeletal muscle. It interacts with mitsugumin 53, annexins, caveolin-3, AHNAK, affixin, S100A10, calpain-3, tubulin and dihydropyridine receptor. Limb-girdle muscular dystrophy 2B (LGMD2B) an...
journal_title:Journal of toxicologic pathology
pub_type: 杂志文章
doi:10.1293/tox.25.135
更新日期:2012-06-01 00:00:00