Effect of dietary retinyl palmitate on the promotion of altered hepatic foci by 3,3′,4,4′-tetrachlorobiphenyl and 2,2′,4,4′,5,5′- hexachiorobiphenyl in rats initiated with diethylnitrosamine

Chen, L.-C.; Robinson, Farrel R.; Glauert, Howard P.; Chow, Ching K.; Robertson, Larry W.

doi:10.1093/carcin/16.2.393

Cited by 19 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As expected, cell proliferation was higher in the PGST-positive foci than in the normal tissue. Previous studies using the same protocol on rats on the same strain, sex and age (Berberian et al 1995;Glauert et al 2005;Tharappel et al 2002) found that cell proliferation in both focal and nonfocal hepatocytes was increased by PCB-77 (unlike our study) but was not affected by PCB-153 (similar result to our study).…”

Section: Discussionsupporting

confidence: 80%

“…DEN was dissolved in saline and administrated by gavage, 150 mg/kg body weight. This dose was chosen based on previous studies (Berberian et al 1995;Glauert et al 2005;Stemm et al 2005;Tharappel et al 2002) Glycine or casein (casein contains 1.8% glycine) was fed in the unrefined diet at 5% starting on the 14th day after DEN initiation until the end of the experiment. Glycine was fed at the 5% level because of previous studies showing that this level inhibited the induction of cell proliferation and hepatic tumors by peroxisome proliferators (Rose et al 1999a;Rose et al 1997a).…”

Section: Experimental Designmentioning

confidence: 99%

See 1 more Smart Citation

The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

et al. 2007

View full text Add to dashboard Cite

Polychlorinated biphenyls (PCBs) are ubiquitious lipophilic environmental pollutants. Some of the PCB congeners and mixtures of congeners have tumor promoting activity in rat liver. The mechanism of their activity is not fully understood and is likely to be multifactorial. The aim of this study was to investigate if the resident liver macrophages, Kupffer cells, are important in the promoting activity of PCBs. The hypothesis of this study was that the inhibition of Kupffer cell activity would inhibit hepatic tumor promotion by PCBs in rats. To test our hypothesis, we studied the effects of Kupffer cell inhibition by dietary glycine (an inhibitor of Kupffer cell secretory activity) in a rat two-stage hepatocarcinogenesis model using 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153, a non-dioxin-like PCB) or 3,3',4,4'-tetrachlorobiphenyl (PCB-77, a dioxin-like PCB) as promoters. Diethylnitrosamine (DEN, 150 mg/kg) was administered to female Sprague Dawley rats, which were then placed on an unrefined diet containing 5% glycine (or casein as nitrogen control) starting two weeks after DEN administration. On the third day after starting the diets, rats received PCB-77 (300 μmol/kg), PCB-153 (300 μmol/kg), or corn oil by i.p. injection. The rats received a total of 4 PCB injections, administered every 14 days. The rats were euthanized on the 10th day after the last PCB injection, and the formation of altered hepatic foci expressing placental glutathione S-transferase (PGST) and the rate of DNA synthesis in these foci and in the normal liver tissue were determined. Glycine did not significantly affect foci number or volume. PCB-153 did not significantly increase the focal volume, but increased the number of foci per liver, but only in the rats not fed glycine; PCB-77 increased both the foci number and their volume in both glycine-fed and control rats. Glycine did not alter the PCB content of the liver, but did increase the activity of 7-benzyloxyresorufin Odealkylase (BROD) in liver microsomes from PCB-153 treated rats. However, glycine did not affect the induction of ethoxyresorufin O-dealkylase activity by PCB-77 in liver microsomes. Glycine diminished hepatocyte proliferation in PGST-positive foci, but not in normal tissue. Overall these results do not support the hypothesis that dietary glycine inhibits the promoting activities of PCBs. The observations that PCB-153 increased the number of foci per liver in control rats but not glycinefed rats and that dietary glycine reduced cell proliferation in PGST-positive foci, however, do not Correspondence to: Howard P. Glauert, Graduate Center for Nutritional Sciences, 222 Funkhouser Building, University of Kentucky, Lexington, KY 40506-0054, Telephone: 859-257-7789, FAX: 859-323-0061, E-Mail: hglauert@uky.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the ...

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Experimental Designmentioning

confidence: 99%

The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In the liver, retinoids have been shown to inhibit both the transformation of hepatic stellate cells [57] and the proliferation of human hepatoma cells [58], while retinol inhibits the development of preneoplastic lesions in the liver of rats treated with chemical carcinogens [59]. Retinol also inhibits the formation of aflatoxin B1 (AFB1) -DNA adducts in hepatocytes [60], which is a known critcal step in aflatoxin-induced hepatocarcinogenesis.…”

Section: Retinoid Metabolismmentioning

confidence: 99%

The Development of Targeted Therapies for Hepatocellular Cancer

Chattopadhyay¹,

Manas²,

Reeves³

2007

CPD

View full text Add to dashboard Cite

Present treatment options for hepatocellular cancer (HCC) are limited to those individuals with good liver function and early stage disease. Unfortunately this includes only a minority of patients, few of which are actually cured of their cancer. Over the last 15-20 years biotechnology has made a very significant impact on medical research, to the extent that we know very much more about the regulation of normal cell growth and death, as well as the mechanisms underlying its disruption in disease processes. This knowledge has and is being rapidly exploited by academic and pharmaceutical organisations, often in collaboration. The result is the development, testing and steady introduction of therapies that target specific abnormalities in cancer cells. Although the safety and effectiveness of the majority of these agents has yet to be established in cirrhotic patients with HCC, we are hopeful that we will shortly see an increase in effective treatment options available for clinical use this disease. This review focuses on aberrant cancer proteins and pathways relevant to HCC, as well as the novel therapies or strategies targeting them, that are currently in the development or testing stages.

show abstract

“…It is known, however, that unlike the coplanar PCBs (like PCB-77), non-coplanar PCBs (like PCB-153) do not act through aryl hydrocarbon receptors (AhR) (Vondracek et al, 2005). PCB-153 and PCB-77 were chosen as representative of the two classes of the PCBs and several studies have shown that these cause many deleterious effects on different organ systems in rodents (Berberian et al, 1995; Glauert et al, 2005; Hemming et al, 1993; Tharappel et al, 2002). It is also known that oxidative stress leads to autism (Chauhan et al, 2004; James et al, 2004), cancer (Nair, 2006; Tas et al, 2005; Valko et al, 2006; Yoshida and Ogawa, 2000) and heart diseases through endothelial damage (Ramadass et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

PCB congener specific oxidative stress response by microarray analysis using human liver cell line

Ghosh

Chatterjee

et al. 2010

Environment International

View full text Add to dashboard Cite

In this study we have examined the effect of exposure to different congeners of PCBs and their role in oxidative stress response. A metabolically competent human liver cell line (HepG2) was exposed with two prototype congeners of PCBs: coplanar PCB-77 and non-coplanar PCB-153. After the predetermined times of exposure (0-24 hours) at 70μM concentration, the HepG2 cells showed significant apoptotic changes by fluorescent microscopy after 12 hours of exposure. Gene set enrichment analysis (GSEA) identified oxidative stress as the predominant enrichment. Further, paraquat assay showed that PCB congeners lead to oxidative stress to different extents, PCB-77 being more toxic. This study, with emphasis on all recommended microarray quality control steps, showed that apoptosis was one of the most significant cellular processes as a result of oxidative stress, but each of these congeners has a unique signature gene expression, which was further validated by Taqman real time PCR and immunoblotting. The pathways involved leading to the common apoptotic effect were completely different. Further in-silico analysis showed that PCB-153 most likely acted through the TNF receptor, leading to oxidative stress involving metallothionein gene families, and causing apoptosis mainly by the Fas receptor signaling pathway. In contrast, PCB-77 acted through the aryl hydrocarbon receptor. It induces oxidative stress through the involvement of cytochrome P450 (CYP1A1) leading to apoptosis through AHR/ARNT pathway.

show abstract

Effect of dietary retinyl palmitate on the promotion of altered hepatic foci by 3,3′,4,4′-tetrachlorobiphenyl and 2,2′,4,4′,5,5′- hexachiorobiphenyl in rats initiated with diethylnitrosamine

Cited by 19 publications

References 0 publications

The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

The Development of Targeted Therapies for Hepatocellular Cancer

PCB congener specific oxidative stress response by microarray analysis using human liver cell line

Contact Info

Product

Resources

About