Dietary Vitamin E Does Not Inhibit the Promotion of Liver Carcinogenesis by Polychlorinated Biphenyls in Rats

Glauert, Howard P.; Lu, Zijing; Kumar, Amita; Bunaciu, Rodica P.; Patel, Sandip; Tharappel, Job C.; Stemm, Divinia N.; Lehmler, Hans‐Joachim; Lee, Eun Y.; Robertson, Larry W.; Spear, Brett T.

doi:10.1093/jn/135.2.283

Cited by 12 publications

(14 citation statements)

References 20 publications

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“…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%

“…The rodent model is considered a very good indicator of potential hepatic damage in humans (Hayes et al 1982) . Seven studies in rats revealed that PCBs promote gross liver tumors and 42 studies demonstrated that PCBs promote altered hepatic foci in rats (Dean et al 2002;Glauert et al 2005;Glauert et al 2001;Tharappel et al 2002;Whysner and Wang 2001).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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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 ...

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Section: Discussionsupporting

confidence: 80%

Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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“…We examined two PCBs: 3,3′ 4,4′-tetrachlorobiphenyl (PCB-77), an Ah receptor agonist; and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153), a CAR activator. PCB-77 did not increase the hepatic DNA binding activity of NF-κB in short-term studies, but did after four biweekly injections (Glauert et al 2005;Lu et al 2003;Tharappel et al 2002). PCB-153, on the other hand, increased the DNA binding activity of NF-κB in short-term studies and in one of two long-term studies (Glauert et al 2005;Lu et al 2004;Lu et al 2003;Tharappel et al 2002).…”

Section: Introductionmentioning

confidence: 89%

“…In the first study, the effect of dietary vitamin E on the hepatic tumor promoting activities of PCB-77 and PCB-153 in female Sprague-Dawley rats (175-200 g) was investigated (Glauert et al 2005). One week after diethylnitrosamine (DEN) injection, rats were fed purified diets containing 10, 50 or 250 mg/kg vitamin E in the form of α-tocopheryl acetate.…”

Section: Vitamin Ementioning

confidence: 99%

Role of oxidative stress in the promoting activities of PCBs

Glauert

Tharappel

et al. 2008

Environmental Toxicology and Pharmacology

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PCBs are organic pollutants that persist and bioaccumulate in the environment. These chemicals induce and promote liver tumors in rodents. Previous studies have shown that they increase oxidative stress in the liver, including lipid peroxidation, oxidative DNA damage, and NF-κB activation. The objective of these studies was to determine if the promoting activities of PCBs could be inhibited by dietary antioxidants (vitamin E, selenium, or phytochemicals) or by knocking out the p50 subunit of NF-κB. In the antioxidant studies, female rats were first injected with DEN (150 mg/kg) and then administered 4 biweekly i.p. injections (300 μmol/kg/injection) of PCB-77, PCB-153, or vehicle; the number and volume of placental glutathione S-transferase (PGST)-positive foci were then quantified. Vitamin E did not influence the promoting activities of PCBs. Increasing dietary selenium above the recommended intake increased the number of foci induced but decreased their volume. Most of the phytochemicals examined (N-acetyl cysteine, β-carotene, resveratrol, EGCG) had no significant effect on the promoting activity of PCB-77. Ellagic acid increased and lycopene decreased the number of foci; ellagic acid, CoQ 10 , and curcumin decreased the volume of foci. In the NF-κB knockout study, male mice were first injected with DEN (90 mg/kg); controls not receiving DEN were also studied. Both p50 −/− and wild-type mice were then injected biweekly 20 times with PCB-153 (300 (μmol/kg). In DEN-treated and DEN + PCB-treated mice, the incidence of tumors was lower in the p50 −/− mice than in wild-type mice. In mice receiving PCB-153, the tumor incidence and tumor volume were higher. The volume of tumors that were positive for glutamine synthetase was increased in mice administered PCB-153. This study shows that the promotion of hepatocarcinogenesis by PCBs is largely unaffected by dietary antioxidants but is diminished when NF-κB activation is impaired by the absence of the p50 subunit.

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Dietary antioxidants in the prevention of hepatocarcinogenesis: A review

Glauert

Calfee-Mason

Stemm

et al. 2010

Mol. Nutr. Food Res.

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In this review, the role of dietary antioxidants in the prevention of hepatocarcinogenesis is examined. Both human and animal models are discussed. Vitamin C, vitamin E, and selenium are antioxidants that are essential in the human diet. A number of non-essential chemicals also contain antioxidant activity and are consumed in the human diet, mainly as plants or as supplements, including beta-carotene, ellagic acid, curcumin, lycopene, coenzyme Q(10), epigallocatechin gallate, N-acetyl cysteine, and resveratrol. Although some human and animal studies show protection against carcinogenesis with the consumption of higher amounts of antioxidants, many studies show no effect or an enhancement of carcinogenesis. Because of the conflicting results from these studies, it is difficult to make dietary recommendations as to whether consuming higher amounts of specific antioxidants will decrease the risk of developing hepatocellular carcinoma.

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Dietary Vitamin E Does Not Inhibit the Promotion of Liver Carcinogenesis by Polychlorinated Biphenyls in Rats

Cited by 12 publications

References 20 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

Role of oxidative stress in the promoting activities of PCBs

Dietary antioxidants in the prevention of hepatocarcinogenesis: A review

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