Superfund Research Program
Arsenic as an Endocrine Disrupter
This project is examining the mechanisms by which exposure to arsenic and chromium contribute to human disease risk. Dr. Hamilton has previously shown that arsenic can act as an endocrine disruptor, blocking the ability of glucocorticoid hormone to signal through its hormone receptor. It has now been demonstrated that similar effects of arsenic on signaling by the estrogen, testosterone and mineralocorticoid receptors in both cell culture and whole animal models. These steroid hormone receptors are all part of the nuclear receptor superfamily, and arsenic may also disrupt other members of this critical family of regulatory proteins, which may be a major contributor to effects of arsenic on vascular disease, diabetes and many different arsenic-associated cancers. Project investigators have also demonstrated a new pathway for chromium signaling in the cell, in which chromium(III), the essential trace element form of chromium, stimulates the cyclic AMP (cAMP) signaling pathway, which in turn contributes to many different cellular responses.