کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2600379 1133260 2011 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ipso substitution of bisphenol A catalyzed by microsomal cytochrome P450 and enhancement of estrogenic activity
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Ipso substitution of bisphenol A catalyzed by microsomal cytochrome P450 and enhancement of estrogenic activity
چکیده انگلیسی

Bisphenol A (BPA), an industrial chemical with estrogenic activity, was investigated as a substrate for the ipso-metabolism catalyzed by microsomal cytochrome P450 (P450). BPA was expected to be transformed to a quinol via an ipso-addition reaction; however, hydroquinone (HQ) was detected as a metabolite via an ipso-substitution reaction. Isopropenylphenol (IPP) and hydroxycumyl alcohol (HCA) were also produced as eliminated metabolites by C-C bond scission via ipso-substitution. Incorporation of the 18O atom to HCA from H218O suggested the presence of a carbocation intermediate. Bulkiness of p-substituted group of BPA and/or stability of the eliminated carbocation intermediate may cause ipso-substitution of BPA. CYP3A4 and CYP3A5 showed higher activity for ipso-substitution. CYP2D6*1 also showed the activity; however, the other 9 isozymes did not. IPP showed ER-binding activity in the same degree of BPA. Furthermore, the ER-binding activity of HCA was about a hundred times greater than that of BPA. These results suggested that this new metabolic pathway contributes to the activation of the estrogenic activity of BPA.

Figure optionsDownload as PowerPoint slideHighlights
► Bisphenol A is transformed to novel metabolites by P450 via ipso-metabolism.
► The novel metabolites were produced by C–C bond scission.
► CYP3A4 and CYP3A5 showed higher activity for ipso-substitution.
► ER-binding activity of one novel metabolite was 100-fold greater than that of BPA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 203, Issue 1, 30 May 2011, Pages 92–95
نویسندگان
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