Morphology and Incidence of Hepatic Foci of Cellular Alteration in Sprague-Dawley Rats

Newsholme, Stephen J.; Fish, C. J.

doi:10.1177/019262339402200507

Cited by 9 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 elaborately. Toxic chemicals like several nitrosamine compounds, used as common food additives, could induce HCC and could cause zonal necrosis of the liver [38,39]. Here, DEN+ CCl 4 induced two types of zonal necrosis.…”

Section: Histological Studymentioning

confidence: 90%

Pharmaceutical efficacy of harmalol in inhibiting hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

Background: Diethylnitrosamine (DEN) promoted by carbon tetrachloride (CCl 4) forms DNA adducts inducing hepatocellular carcinoma (HCC). Plant alkaloid, harmalol, is being used as a therapeutic agent against HCC due to its accessibility and efficacy by apoptosis and inhibiting proliferation of cancer epithelial cells. Result: Seven groups of Swiss albino mice were taken. Different stages of liver tissues and serum from various experimental groups were collected before and after harmalol treatment. The investigation was carried out by enzyme assay, bilirubin level in the blood, DNA, RNA, normal serum protein of liver tissue, and alpha-feto protein estimation of serum. Gross morphological assessment of liver, histological, and different apoptosis markers viz. p53, caspase3, and cytochrome C expression were analyzed by RT-PCR and Western blot. Harmalol (10 mg/kg B.W. per week, I.P.) for 9 weeks showed a significant reduction in hepatocellular foci, nodules, and carcinoma ultimately retaining the normal morphology. It further induces ROS-dependent apoptosis through mitochondrial cytochrome C release that induces p53 by caspase3 activation. Conclusion: The investigation will eventually help to develop more effective chemotherapeutic drugs from the natural source.

show abstract

Section: Histological Studymentioning

confidence: 90%

Pharmaceutical efficacy of harmalol in inhibiting hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It was well known that there are strain and species differences in susceptibility to liver tumor induction (Newsholme and Fish, 1994; Moennikes et al, 1999; van Ravenzwaay and Tennekes, 2002). The C57BL/6 strain, which is the background of both the Cx32 deficient and Cx32 dominant negative mutant transgenic mice, has low susceptibility with regard to spontaneous and chemical induction tumors, for example as compared with the C3H strain (Moennikes et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Transgenic Disruption of Gap Junctional Intercellular Communication Enhances Early but Not Late Stage Hepatocarcinogenesis in the Rat

et al. 2005

View full text Add to dashboard Cite

Much experimental evidence supports the conclusion that loss of gap junctional intercellular communication (GJIC) contributes to carcinogenesis. Transgenic rats featuring a dominant negative mutant of the connexin 32 gene under albumin promoter control (Cx32 Tg-High and Cx32 Tg-Low lines, respectively with high and low copy numbers of the transgene) have disrupted GJIC, as demonstrated by scrape dye-transfer assay in vivo as previous report by Asamoto et al. (2004). In the present study, we investigated the susceptibility of these transgenic rats to a single intraperitoneal administration of diethylnitrosamine (DEN), and found a significant increase in preneoplastic glutathione S-transferase placental form (GST-P) positive lesions in the livers of Cx32 Tg-High but not Cx32 Tg-Low rats. However, incidences of adenomas and hepatocellular carcinomas were not elevated at the end of the experiment (52 weeks). In addition, we investigated the promotional effect of phenobarbital (PB) on Cx32 Tg-High rats pretreated with DEN and found enhanced formation of GST-P positive lesions, in contrast to the lack of promoting effects reported for Cx32 deficient mice. The results indicate that although both high and low expression of the dominant negative connexin 32 mutant gene in our rats is able to inhibit gap junctional capacity, only high expression is effective at enhancing susceptibility to early stage DEN-induced liver carcinogenesis.

show abstract

“…Since the incidence of spontaneous hepatocellular tumors is still low even in rats maintained for their entire lifetime 14 , it is considered that most spontaneous foci do not progress to neoplasia in rats. Classification of hepatic foci by phenotype indicates that the spontaneous incidence of tigroid basophilic foci is high in rats, whereas diffusely basophilic and amphophilic foci are very rare [13][14][15][16] . However, these diffusely basophilic and amphophilic foci have been shown to increase significantly in rats treated with various genotoxic hepatocarcinogens 17,18 .…”

Section: Focus Of Cellular Alterationmentioning

confidence: 99%

A Review of Nomenclature and Diagnostic Criteria for Proliferative Lesions in the Liver of Rats by a Working Group of the Japanese Society of Toxicologic Pathology.

et al. 2003

View full text Add to dashboard Cite

Abstract:The final version of the international harmonized nomenclature for proliferative lesions in rats was issued on June 21, 2000. The recommended nomenclature for proliferative lesions in the liver includes focus of cellular alteration, regenerative hepatocellular hyperplasia, cholangiofibrosis, cholangiofibroma, oval cell hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, bile duct hyperplasia, cholangioma, cholangiocarcinoma, hepatocholangiocellular adenoma, and hepatocholangiocellular carcinoma. Foci of cellular alteration are further classified into the following phenotypes: amphophilic, diffusely basophilic, tigroid basophilic, clear cell, eosinophilic, and mixed (basophilic/eosinophilic). Hepatocellular carcinomas are divided into 3 types based on their growth patterns: acinar, solid, and trabecular. In consideration of this international harmonized nomenclature, the current classification, terminology, and diagnostic criteria for prolifrative lesions in the liver of rats recommended by the Japanese Society of Toxicologic Pathology (JSTP) were reviewed by a Working Group of the JSTP. The hepatic proliferative lesions reviewed by the present Working Group included lesions of hepatocellular, cholangiocellular, mixed hepatocholangiocellular, sinusoidal, and hemangioendothelial origins. Any comments and questions on these lesions were discussed among pathologists in the Working Group and the results of discussions were presented at the 1st seminar on the continuing education program

show abstract

Morphology and Incidence of Hepatic Foci of Cellular Alteration in Sprague-Dawley Rats

Cited by 9 publications

References 10 publications

Pharmaceutical efficacy of harmalol in inhibiting hepatocellular carcinoma

Pharmaceutical efficacy of harmalol in inhibiting hepatocellular carcinoma

Transgenic Disruption of Gap Junctional Intercellular Communication Enhances Early but Not Late Stage Hepatocarcinogenesis in the Rat

A Review of Nomenclature and Diagnostic Criteria for Proliferative Lesions in the Liver of Rats by a Working Group of the Japanese Society of Toxicologic Pathology.

Contact Info

Product

Resources

About