Morizane Miwa, Kawasaki Yoichi, Miura Taro, Yagi Kenta, Esumi Satoru, Kitamura Yoshihisa, Sendo Toshiaki
a Department of Pharmacy , Okayama University Hospital , Okayama , Japan.
J Toxicol Environ Health A. 2015;78(23-24):1450-60. doi: 10.1080/15287394.2015.1094431.
A recent in vitro study reported that the photoinitiator 2-isopropylthioxanthone (2-ITX) is an endocrine-disrupting compound (EDC). However, it is not clear whether other photoinitiators such as 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) produce endocrine-disrupting effects. The purpose of this study was thus to assess the association between estrogenic activity and exposure to photoinitiators. For estimation of the proliferative effect of the photoinitiators, the E-screen assay was used. Six photoinitiators, 2,2-dimethoxy-2-phenylacetophenone (2,2-DMPAP), 2-ethylhexyl 4-(dimethylamino)benzoate (2-EHDAB), 1-HCHPK, 2-ITX, methyl-2-benzoylbenzoate (MBB), and MTMP, significantly increased number of MCF-7 cells, an estrogen-sensitive human breast cancer cell line. In addition, pretreatment with estrogen receptor (ER) antagonists such as clomiphene, tamoxifen, or fulvestrant, significantly reversed the proliferative effect of each photoinitiator. Data demonstrated that the six photoinitiators produced endocrine-disrupting effects and that these photoinitiators interacted with ER as agonists. Evidence indicates that the six photoinitiators demonstrated estrogenic activity via ER as agonists.
最近的一项体外研究报告称,光引发剂2-异丙基噻吨酮(2-ITX)是一种内分泌干扰化合物(EDC)。然而,尚不清楚其他光引发剂,如1-羟基环己基苯基酮(1-HCHPK)和2-甲基-4'-(甲硫基)-2-吗啉代苯丙酮(MTMP)是否会产生内分泌干扰作用。因此,本研究的目的是评估雌激素活性与光引发剂暴露之间的关联。为了评估光引发剂的增殖作用,使用了E-筛选试验。六种光引发剂,2,2-二甲氧基-2-苯基苯乙酮(2,2-DMPAP)、2-乙基己基4-(二甲基氨基)苯甲酸酯(2-EHDAB)、1-HCHPK、2-ITX、甲基-2-苯甲酰苯甲酸(MBB)和MTMP,显著增加了雌激素敏感的人乳腺癌细胞系MCF-7细胞的数量。此外,用克罗米芬、他莫昔芬或氟维司群等雌激素受体(ER)拮抗剂进行预处理,可显著逆转每种光引发剂的增殖作用。数据表明,这六种光引发剂产生了内分泌干扰作用,并且这些光引发剂作为激动剂与ER相互作用。有证据表明,这六种光引发剂作为激动剂通过ER表现出雌激素活性。