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

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

Toxicology and applied pharmacology (2014-03-04)
Qiuli Shan, Jing Wang, Fengchen Huang, Xiaowen Lv, Min Ma, Yuguo Du
ABSTRACT

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(-/-) 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(-/-) mice. Significantly, our observations suggest that combined exposure to TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies.

MATERIALS
Product Number
Brand
Product Description

Supelco
Aroclor 1254 solution, certified reference material, 1000 μg/mL in isooctane
Supelco
Aroclor 1254 solution, certified reference material, 500 mg/kg in transformer oil
Supelco
Aroclor 1254 solution, certified reference material, 50 mg/kg in transformer oil
Supelco
Aroclor 1254 solution, certified reference material, 200 μg/mL in methanol
Supelco
Aroclor 1254, ampule of 50 mg, analytical standard
Supelco
Aroclor 1254 solution, certified reference material, 1000 μg/mL in methanol