Assessment of the alleged estrogen receptor-mediated activity of phthalate esters
- Univ. of Western Ontario, London, Ontario (Canada). Dept. of Pharmacology and Toxicology
The alleged estrogen receptor (ER)-mediated activities of eight phthalate esters (i.e., di-2-ethyl hexyl, di-n-butyl (DBPE), butyl benzyl (BBPE), di-hexyl (DHPE), diisoheptyl, di-n-octyl, diiso-nonyl, diiso-decyl) were investigated in several in vitro bioassays. Results from recombinant receptor/reporter gene assays consisting of MCF-7 human breast cancer cells transiently transfected with the Ga14-human estrogen receptor construct, Ga14-HEGO, and the Ga14-regulated luciferase reporter gene, 17m5-G-Luc, have shown that 10 {micro}M of DBPE, BBPE, or DHPE exhibited 36, 42, and 20% activity, respectively, when compared to the 100% response induced by the standard, 1 nM 17{beta}-estradiol (E2). However, these increases, while statistically significant, are not sufficient to conclude that DBPE, BBPE, or DHPE are estrogenic. No significant increase in luciferase activity was observed with the five remaining phthalate esters. In preliminary studies, only BBPE was found to (1) induce luciferase activity in HeLa human uterine cells stably transfected with Ga14-HEGO and 17m5-G-Luc constructs, (2) increase MCF-7 cell proliferation, and (3) impart ER-mediated viability to the E2-dependent recombinant yeast strain, PL3, on selective media. However, of the four in vitro responses elicited by BBPE, only MCF-7 cell proliferation was greater than 50%. In addition, the ability of in vitro assays to identify chemicals that are capable of inducing increases in uterine wet weight and vaginal cell cornification in rodents will be discussed. Therefore, these studies will assess the alleged ER-mediated activity of phthalate esters and correlate in vitro assays to responses elicited in vivo.
- OSTI ID:
- 460508
- Report Number(s):
- CONF-961149--
- Country of Publication:
- United States
- Language:
- English
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