A possible pathogenesis for Blackfoot disease--effects of trivalent arsenic (As2O3) on cultured human umbilical vein endothelial cells.
Blackfoot disease (BFD) is an endemic peripheral vascular occlusive disease found among the inhabitants of the southwest coast of Taiwan. The clinical features of BFD are similar to those of Buerger's disease. Pathology shows arteriosclerosis obliterans and thromboangiitis obliterans. The high arsenic content of artesian well water in the area is regarded as the main causal factor of this disease. Therefore, the purpose of this study was to observe the toxic effects of various arsenic concentrations on cultured human umbilical vein endothelial cells (HUV-EC). The methods of this study included cell growth assay, 51Cr-release assay, and staining of Factor VIII related antigen (FVIII-RAg) and Ulex europaeus agglutinin I (UEA-I) binding sites of HUV-EC. The following data were obtained: 1) no obvious cytotoxicity in 51Cr-release assay; 2) inhibition of the synthesis of both FVIII-RAg and UEA-I binding sites when the arsenic concentration was above 100 ng/ml; 3) dose-dependent inhibition of growth of HUV-EC by any concentration of arsenic. At a higher concentration of more than 100 ng/ml, arsenic inhibited endothelial cell proliferation and glycoprotein synthesis, whereas it only inhibited the proliferation at a lower concentration of less than 50 ng/ml. It is suggested that arsenic, at both higher and lower concentrations, may damage endothelial cells. Such damage may play an important role in the pathogenesis of BFD.
Chen
G S
GS
Department of Dermatology, Kitasato University School of Medicine, Sagamihara, Japan.
Asai
T
T
Suzuki
Y
Y
Nishioka
K
K
Nishiyama
S
S
D001151:Arsenic / Q000009:adverse effects / Q000633:toxicity*; D001157:Arterial Occlusive Diseases / Q000139:chemically induced* / Q000453:epidemiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002840:Chromates / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D037102:Lectins / Q000378:metabolism; D037121:Plant Lectins; D013624:Taiwan / Q000453:epidemiology; D014471:Umbilical Veins; D014841:von Willebrand Factor / Q000032:analysis
D002840:Chromates; D037102:Lectins; D037121:Plant Lectins; C036850:Ulex europaeus lectins; D014841:von Willebrand Factor; D001151:Arsenic