کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2603818 1133838 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Application of a metabolizing system as an adjunct to the rat whole embryo culture
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Application of a metabolizing system as an adjunct to the rat whole embryo culture
چکیده انگلیسی

Rodent post-implantation whole embryo culture (WEC) is a validated and widely used method in both mechanistic studies and as a screening test for developmental toxicants. Since metabolism is lacking in the WEC because of the developmental stage of the embryo, pro-teratogenic compounds are not detected.We investigated the inclusion of an in vitro metabolizing system as a pre-incubation step in the existing WEC.We started by testing cyclophosphamide, a known pro-teratogen. Without metabolic activation, cyclophosphamide is not teratogenic to rat embryos, as evidenced by a lack of effect on either embryonic growth or on morphological development. After pre-incubation with Aroclor-induced hepatic microsomes, cyclophosphamide became highly embryotoxic in the WEC. We tested five additional compounds to prevalidate this method: valpromide, 2-acetylaminofluorene, 2-methoxyethanol, retinol, and benzo[a]pyrene. Results revealed that not all of these five compounds underwent (complete) metabolic activation. This is probably due to the fact that microsomes do not contain the full spectrum of hepatic enzymes. Attempts have been made to replace microsomes by S9 liver fractions, which do contain microsomal enzymes as well as a series of cytoplasmic enzymes. However, S9 appeared to be extremely toxic in the WEC. Future experiments have to be performed to explore alternative ways of complete metabolic activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 22, Issue 5, August 2008, Pages 1332–1336
نویسندگان
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