Formation of estrogenic products from environmental phthalate esters under light exposure.
Phthalate esters (PEs) have been suspected to be environmental endocrine disruptors and the detailed mechanism remains unclear. The activities of these chemicals can be enhanced through chemical modification under the environmental conditions. We demonstrate that PEs acquire unequivocal estrogenic activity by light exposure. Through UV exposure of an aqueous PE solution, one active photoproduct, identified as 4-hydroxyPE (PE-4OH) based on its characteristic UV and mass spectra, was detected in an estrogen receptor alpha-dependent transactivation assay. PE-4OH was effectively generated by UV 290 nm. The PE-4OH production accompanied H2O2 generation in a UV dose-dependent manner. Both PE and UV irradiation were indispensable in the generation of H2O2. Addition of H2O2 to the PE solution increased PE-4OH production under UV irradiation. The PE-4OH production was also observed in the PE reaction with the Fenton reagent generating hydroxyl radical without UV irradiation. The proposed mechanism for PE-4OH production based on these results is such that by PE-mediated photosensitization H2O2 is generated from O2 and H+ and decomposed to hydroxyl radical, thus oxidizing the PE benzene ring. The PEs-4OH are remarkably active estrogenic products of PEs and would be involved in ER-mediated endocrine disruption.
Okamoto
Yoshinori
Y
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.
Hayashi
Tomohiro
T
Toda
Chitose
C
Ueda
Koji
K
Hashizume
Kiyomatsu
K
Itoh
Kazuo
K
Nishikawa
Jun-ichi
J
Nishihara
Tsutomu
T
Kojima
Nakao
N
D002851:Chromatography, High Pressure Liquid; D004785:Environmental Pollutants; D004952:Esters / Q000737:chemistry; D004967:Estrogens / Q000138:chemical synthesis*; D006861:Hydrogen Peroxide / Q000032:analysis; D006900:Hydroxylation; D008027:Light; D013058:Mass Spectrometry; D010777:Photochemistry; D010795:Phthalic Acids / Q000737:chemistry*
D004785:Environmental Pollutants; D004952:Esters; D004967:Estrogens; D010795:Phthalic Acids; D006861:Hydrogen Peroxide