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Title: Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants found as complex mixtures in the environment throughout the world. Therefore, humans are ubiquitously and simultaneously exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to atherosclerosis. However, the effects of interactions or synergism between TCDD and PCBs on atherogenesis are unknown. We investigated the possible enhanced atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s) involved in this enhancement. Male ApoE{sup −/−} mice were exposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over six weeks of duration. Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone, developed atherosclerotic lesions. Moreover, we found that atherosclerotic disease was exacerbated to the greatest extent in mice co-exposed to TCDD and Aroclor1254. The enhanced lesions correlated with several pro-atherogenic changes, including a marked increase in the accumulation of the platelet-derived chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and Aroclor1254 markedly enhanced atherogenesis in ApoE{sup −/−} mice. Significantly, our observations suggest that combined exposure tomore » TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies. - Highlights: • Augmented atherogenesis was found in ApoE{sup −/−} mice co-exposed to Aroclor1254 and TCDD. • Enhanced expression of PF4, MCP-1 and RIG-I correlated with augmented lesions. • POPs combination may be a greater cardiovascular health risk than individual POPs.« less
Authors:
 [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [1]
  1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)
  2. Feed Safety Reference Laboratory of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Zhongguancun South Street 12, Beijing 100081 (China)
  3. Laboratory of Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)
Publication Date:
OSTI Identifier:
22439698
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 276; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARTERIOSCLEROSIS; DIOXIN; ENVIRONMENT; GENES; GLOBAL ASPECTS; HEALTH HAZARDS; IMMUNITY; INTRAPERITONEAL INJECTION; MICE; POLLUTANTS; POLYCHLORINATED BIPHENYLS