Arsenic as an endocrine disruptor: Effects of arsenic on estrogen receptor-mediated gene expression in vivo and in cell culture
Davey, JC; Bodwell, JE; Gosse, JA; Hamilton, JW
HERO ID
626968
Reference Type
Journal Article
Year
2007
Language
English
PMID
| HERO ID | 626968 |
|---|---|
| In Press | No |
| Year | 2007 |
| Title | Arsenic as an endocrine disruptor: Effects of arsenic on estrogen receptor-mediated gene expression in vivo and in cell culture |
| Authors | Davey, JC; Bodwell, JE; Gosse, JA; Hamilton, JW |
| Journal | Toxicological Sciences |
| Volume | 98 |
| Issue | 1 |
| Page Numbers | 75-86 |
| Abstract | 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 disease; 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 experimental animal and cell culture systems at much lower levels. We previously reported that As is a potent endocrine disruptor, altering gene regulation by the closely related glucocorticoid, mineralocorticoid, progesterone and androgen steroid receptors at concentrations as low as 0.01 µM ( 0.7 ppb). Very low doses enhanced hormone-mediated gene transcription whereas slightly higher but still non-cytotoxic doses were suppressive. We report here that As also disrupts the more distally related estrogen receptor (ER) both in vivo and in cell culture. At non-cytotoxic doses (1-50 µmol/kg arsenite) As strongly suppressed ER-dependent gene transcription of the 17ß-estradiol (E2)-inducible vitellogenin II gene in chick embryo liver in vivo. In cell culture, non-cytotoxic levels (0.25-3 µM, 20-225 ppb) of As significantly inhibited E2-mediated gene activation of an ER-regulated reporter gene and the native ER-regulated GREB1 gene in human breast cancer MCF-7 cells. While the effects of As on ER-dependent gene regulation were generally similar to As effects on the other steroid receptors, there were specific differences, particularly the lack of significant enhancement at the lowest doses, that may provide insights into possible mechanisms. |
| Doi | 10.1093/toxsci/kfm013 |
| Pmid | 17283378 |
| Wosid | WOS:000247601800007 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | |WOS:000247601800007 |
| Is Public | Yes |
| Language Text | English |
| Keyword | arsenic (As); estrogen receptor (ER); steroid receptors (SR); GREB1 |
| Is Qa | No |