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Polychlorinated biphenyls alter the expression of endothelial nitric oxide synthase mRNA in human umbilical vein endothelial cells

Department of Plastic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan, Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

Hideki Fukata

Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan, Environmental Health Science Project for Future Generations, Graduate School of Medicine, Chiba University, Chiba, Japan

Koji Sato

Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

Koji Yamazaki

Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

Keiko Aida-Yasuoka

Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

Hidetaka Takigami

Research Center for Material Cycles and Waste Management, National Institute for Environmental Studies, Ibaraki, Japan

Motone Kuriyama

Department of Plastic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan, Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan

Masaharu Ichinose

Department of Plastic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

Chisato Mori

Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan, Environmental Health Science Project for Future Generations, Graduate School of Medicine, Chiba University, Chiba, Japan, cmori{at}faculty.chiba-u.jp

Polychlorinated biphenyls (PCBs) are a group of persistent pollutants that are detected in maternal serum and umbilical cord, suggesting that fetal exposure also needs to be considered. The effects of dioxin-like PCB congeners 3,3',4,4'-tetrachlorobiphenyl (PCB77) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) and a non-dioxin-like compound 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) on the expression of endothelial nitric oxide synthase (eNOS), known to maintain blood flow to the fetus, in human umbilical vein endothelial cells (HUVECs) were investigated. The mRNA levels of eNOS, aryl hydrocarbon receptor (AhR) and cytochrome P450 (CYP) 1A1 in cells treated with 5 µM PCBs for 24 hours were analysed by real-time RT-PCR. Cells were also treated with -naphthoflavone ( NF), an AhR antagonist or ICI 182780, an estrogen receptor (ER) antagonist, one hour prior to PCB exposure, to observe the effects of these receptors on eNOS modulation. Each PCB increased the eNOS mRNA level by 4.5-fold that was markedly inhibited by NF. ERs were also suspected of altering eNOS levels because ICI 182780 treatment resulted in a decrease in the eNOS level. These results suggest that the eNOS mRNA expression increases due to the action of PCBs related to both AhR and ERs in HUVECs, and that maternal PCB exposure could influence fetal circulation. Human & Experimental Toxicology (2007) 26, 811—816

Key Words: aryl hydrocarbon receptor (AhR) • endothelial nitric oxide synthase (eNOS) • estrogen receptors (ERs) • human umbilical vein endothelial cells (HUVECs) • polychlorinated biphenyls (PCBs)

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