Arsenic as an Endocrine Disruptor: Effects of Arsenic on Estrogen Receptor–Mediated Gene Expression In Vivo and in Cell Culture

Arsenic (As) contamination of drinking water is considered a serious worldwide environmental health threat that is associated with increased disease risks including skin, lung, bladder, and other cancers; type 2 diabetes; vascular and cardiovascular dis-eases; reproductive and developmental effects; and neurological and cognitive effects. Increased health risks may occur at as low as 10–50 ppb, while biological effects have been observed in exper-imental animal and cell culture systems at much lower levels. We previously reported that As is a potent endocrine disruptor, alter-ing gene regulation by the closely related glucocorticoid, miner-alocorticoid, progesterone, and androgen steroid receptors (SRs) at concentrations as low as 0.01mM ( ~ 0.7 ppb). Very low doses enhanced hormone-mediated gene transcription, whereas slightly higher but still noncytotoxic doses were suppressive. We report here that As also disrupts the more distally related estrogen re