Formation of estrogenic products from benzophenone after exposure to sunlight.
Benzophenone (BP) is a suspected endocrine disrupter that is found in our environment. BP undergoes metabolic and photochemical activation. In this study, photoproducts of BP were identified using high-performance liquid chromatography and mass spectrometry and their estrogenic activity was determined using both in vitro and in vivo assays. Although BP showed no estrogenic activity, two estrogenic photoproducts were detected after irradiating an aqueous solution of BP with UV or sunlight. These active products were identified as 3-hydroxy BP (BP-3OH) and 4-hydroxyBP (BP-4OH). The formation of hydrogen peroxide H2O2) was detected with increasing levels of UV, and the addition of H2O2 to the BP solution increased BP-3OH and BP-4OH production under UV irradiation. BP hydroxylation was also observed in the reaction with the Fenton reagent generating hydroxyl radical without UV irradiation. These results suggest the involvement of photochemically generated H2O2 and hydroxyl radical in the BP hydroxylation. BP-4OH was more potent than BP-3OH for promoting estrogen receptor (ER)-mediated transcription and uterotrophic activity, although both of them showed same affinity in ER binding. In conclusion, BP can be converted into ring-hydroxylated derivatives that have estrogenic activity after exposure to light.
Hayashi
Tomohiro
T
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Nagoya, Japan.
Okamoto
Yoshinori
Y
Ueda
Koji
K
Kojima
Nakao
N
D000818:Animals; D001577:Benzophenones / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D002851:Chromatography, High Pressure Liquid; D004968:Estrogens, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D005260:Female; D006861:Hydrogen Peroxide / Q000032:analysis; D006900:Hydroxylation; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013472:Sunlight; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D014599:Uterus / Q000187:drug effects; D015003:Yeasts / Q000378:metabolism
D001577:Benzophenones; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D006861:Hydrogen Peroxide