Role of oxidative stress in the promoting activities of PCBs
Role of oxidative stress in the promoting activities of PCBs
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DOI：
10.1016/j.etap.2007.10.025
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发表时间：
2008-03-01
影响因子：
4.3
通讯作者：
Spear, Brett T.
中科院分区：
文献类型：
--
作者：
Glauert, Howard P.;Tharappel, Job C.;Spear, Brett T.
多氯联苯是一种有机污染物，可在环境中持续存在并进行生物积累。这些化学物质在啮齿类动物中诱发和促进肝脏肿瘤。先前的研究表明，它们会增加肝脏的氧化应激，包括脂质过氧化、DNA氧化损伤和nf - κ B活化。这些研究的目的是确定饮食抗氧化剂（维生素E、硒或植物化学物质）或敲除NF-kappa b的p50亚基是否可以抑制多氯联苯的促进活性。在抗氧化研究中，雌性大鼠首先注射DEN (150 mg/kg)，然后每两周注射4次多氯联苯77、多氯联苯153或载体（300 μ mol/kg/注射）；测定胎盘谷胱甘肽s -转移酶（PGST）阳性灶的数量和体积。维生素E对多氯联苯的促进作用没有影响。饲粮中硒含量高于推荐摄取量时，引起的病灶数量增加，但体积减小。大多数植物化学物质（n -乙酰半胱氨酸、β -胡萝卜素、白藜芦醇、EGCG）对PCB-77的促进作用不显著。鞣花酸增加了斑点数量，番茄红素减少了斑点数量；鞣花酸、CoQ（10）和姜黄素降低了病灶的体积。在NF-kappa B敲除研究中，雄性小鼠首先注射DEN (90 mg/kg)；未接受DEN治疗的对照组也进行了研究。p50 -/-和野生型小鼠每两周注射20次PCB-153 （300 μ mol/kg）。在DEN处理和DEN + pcb处理的小鼠中，p50 -/-小鼠的肿瘤发生率低于野生型小鼠。在接受PCB-153的小鼠中，肿瘤发生率和肿瘤体积更高。在给药PCB-153的小鼠中，谷氨酰胺合成酶阳性的肿瘤体积增加。这项研究表明，多氯联苯促进肝癌的发生在很大程度上不受饮食抗氧化剂的影响，但当NF-kappa B的激活因缺乏p50亚基而受损时，这种促进作用就会减弱。(C) 2007 Elsevier B.V.版权所有
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-kappa B 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-kappa B. In the antioxidant studies, female rats were first injected with DEN (150 mg/kg) and then administered four biweekly i.p. injections (300 mu mol/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, beta-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-kappa B 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 mu mol/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-kappa B activation is impaired by the absence of the p50 subunit. (C) 2007 Elsevier B.V. All rights reserved.