Arsenic Stimulates Angiogenesis and Tumorigenesis In Vivo

currently being used to treat hematologic tumors and is being investigated for treating solid tumors. However, low concentra-tions of As(III) stimulate vascular cell proliferation in cell culture, although this has not been confirmed in vivo. Therefore, the hy-pothesis that As(III) enhances blood vessel growth (angiogenesis) and tumorigenesis was tested in two in vivo models of angiogenesis and a model of tumor growth. In the first, arsenite caused a dose-dependent increase in vessel density in a chicken chorioallan-toic-membrane (CAM) assay. The threshold As(III) concentration for this response was 0.033 M and inhibition of vessel growth was observed at concentrations greater than 1 M. Mouse Matrigel implants were used to test the angiogenic effects of As(III) in an adult mammalian system. Mice were injected with 0.8–80 g/kg As(III)/day over a three-week period. During the last two weeks, Matrigel plugs were placed on the abdominal wall. Low and hig