Effect of Dietary Selenium on the Promotion of Hepatocarcinogenesis by 3,3′, 4,4′-Tetrachlorobiphenyl and 2,2′, 4,4′, 5,5′-Hexachlorobiphenyl

Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that have promoting activity in the liver. PCBs induce oxidative stress, which may influence carcinogenesis. Epidemiological studies strongly suggest an inverse relationship between dietary selenium (Se) and cancer. Despite evidence linking Se deficiency to hepatocellular carcinoma and liver necrosis, the underlying mechanisms for Se cancer protection in the liver remain to be determined. We examined the effect of dietary Se on the tumor promoting activities of two PCBs congeners, 3,3', 4,4'-tetrachlorobiphenyl (PCB-77) and 2,2', 4,4', 5,5'-hexachlorobiphenyl (PCB-153) using a 2-stage carcinogenesis model. An AIN-93 torula yeast-based purified diet containing 0.02 (deficient), 0.2 (adequate), or 2.0 mg (supplemental) selenium/kg diet was fed to Sprague-Dawley female rats starting ten days after administering a single dose of diethylnitrosamine (150 mg/kg). After being fed the selenium diets for 3 weeks, rats received four i.p. injections of either PCB-77 or PCB-153 (150 micromol/kg) administered every 14 days. The number of placental glutathione S-transferase (PGST)-positive foci per cm(3) and per liver among the PCB-77-treated rats was increased as the Se dietary level increased. Unlike PCB-77, rats receiving PCB-153 did not show the same Se dose-response effect; nevertheless, Se supplementation did not confer protection against foci development. However, the 2.0 ppm Se diet reduced the mean focal volume, indicating a possible protective effect by inhibiting progression of preneoplastic lesions into larger foci. Cell proliferation was not inhibited by Se in the liver of the PCB-treated groups. Se did not prevent the PCB-77-induced decrease of hepatic Se and associated reduction in glutathione peroxidase (GPx) activity. In contrast, thioredoxin reductase (TrxR) activity was not affected by the PCBs treatment or by Se supplementation. These findings indicate that Se does not inhibit the number of PGST-positive foci induced during promotion by PCBs, but that the size of the lesions may be inhibited. The effects of Se on altered hepatic foci do not correlate with its effects on GPx and TrxR.

Acute toxicity of 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) in male Sprague–Dawley rats: Effects on hepatic oxidative stress, glutathione and metals status

“…SeGPx and thioredoxin reducase, certainly signifies an alteration in the redox balance of the cells. Reduction in hepatic Se levels was also reported previously after treatment with PCB 77 (Stemm et al 2008) and TCDD (Hassan et al 1985). The mechanism by which hepatic selenium is lost following exposure to AhR agonists is currently unknown and under investigation.…”

Effect of antioxidant phytochemicals on the hepatic tumor promoting activity of 3,3′,4,4′-tetrachlorobiphenyl (PCB-77)

“…Only one of the PCBs that have promoting activity in the liver was studied, however, so it is possible that one or more of these phytochemicals could have a major effect on another PCB that has promoting activity. The results of this study, in combination with the studies showing that vitamin E and selenium also do not clearly decrease the promoting activities of PCB-77 and PCB-153 (Glauert et al , 2005; Stemm et al , 2008), imply that dietary antioxidants are not effective at inhibiting tumor promotion by PCBs. These results also indicate that the induction of oxidative stress by PCBs may not be a mechanism in the promoting activities of these agents.…”

“…Stemm et al (2008) found that selenium supplementation increased the number of PGST-positive foci in PCB-77-treated rats, but that it reduced the mean focal volume of the foci in untreated, PCB-77-treated, and PCB-153-treated rats. Glauert et al (2005) found that dietary vitamin E did not affect the promotion of PGST-positive foci by either PCB-77 or PCB-153.…”

“…A number of other agents have been observed to have opposite effects on focal number and focal size. Stemm et al (2008) found that dietary selenium increased the number of foci but decreased their size in PCB-treated rats. Kobusch et al (1989), however, found that PCB-77 increased the size of N-nitrosomorpholine-initiated foci but decreased the number induced.…”

Dietary antioxidants (selenium and N-acetylcysteine) modulate paraoxonase 1 (PON1) in PCB 126-exposed rats

“…Although this change in PON1 should enhance protection against cardiovascular diseases, PCB 126 was linked to increased risk for atherosclerosis (Hennig et al 2002a; Hennig et al 2002b). PCB 126 also disrupted the homeostasis of antioxidants such as selenium (Hassan et al 1985; Lai et al 2011; Stemm et al 2008), an element that appears to be protective for high-density lipoprotein (HDL)-associated enzymes like PON1 (Kaur and Bansal 2009). In addition, PCB 126 depleted GSH (Hassoun and Periandri-Steinberg 2010) which may place the free –SH group in PON1 at increased risk of oxidation.…”