An In Vivo Bioassay for Detecting Antiandrogens Using Humanized Transgenic Mice Coexpressing the Tetracycline-Controlled Transactivator and Human CYP1B1 Gene
| Autor: | Yhun Yhong Sheen, Seung Wan Jee, Yong K. Kim, Dae Y. Hwang, Su J. Seo, Jung S. Cho, Su H. Lee, Jae H. Oh, Hyun Gu Kang, Sun B. Shim, Seok H. Lee |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Antiandrogens medicine.drug_class CYP1B1 Transgene Blotting Western Gene Expression Mice Transgenic 010501 environmental sciences Biology Pharmacology Toxicology Antiandrogen 030226 pharmacology & pharmacy 01 natural sciences Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P-450 Enzyme System In vivo Internal medicine medicine Animals Humans Bioassay Transgenes Promoter Regions Genetic 0105 earth and related environmental sciences Reverse Transcriptase Polymerase Chain Reaction Phthalate Androgen Antagonists Tetracycline Blot Endocrinology chemistry Cytochrome P-450 CYP1B1 Trans-Activators Aryl Hydrocarbon Hydroxylases |
| Zdroj: | International Journal of Toxicology. 24:157-164 |
| ISSN: | 1092-874X 1091-5818 |
| DOI: | 10.1080/10915810590948370 |
| Popis: | The typical strategy used in analysis of antiandrogens involves the morphological changes of a marker in castrated rats Hershberger assay for the prostate, seminal vesicle, levator ani plus bulbocavernosus muscles (LABC), Cowper’s gland, and glans penis. However, there are disadvantages to this approach, such as the time required, and the results may not correspond to those in actual human exposure. To evaluate its ability for detecting antiandrogens, in vivo the dose effect of di-(2-ethylhexyl) phthalate (DEHP) and time effect of five antiandrogens, DEHP, di-n-butyl phthalate (DBP), diethyl phthalate (DEP), linuron (3-(4-dichlorophenyl)-methoxy-1-methylurea), and 2,4′-DDE (1,1-dichloro-2-( p-chlorophenyl)-2-( o-chlorophenyl)ethylene), were investigated using humanized transgenic mice coexpressing tetracycline-controlled transactivator (tTA) and the human cytochrome P450 (CYP) enzyme CYP1B1 (hCYP1B1). Adult transgenic males were treated with each of the five antiandrogens, and their tTA-driven hCYP1B1 expressions analyzed by real-time polymerase chain reaction (PCR) and/or Western blot and for O-debenzylation activity. Herein, the treatments of adult males with the five antiandrogens were shown to affect the increased levels of tTA-driven hCYP1B1 expression in both dose-dependent and repeated experiments. Thus, this novel in vivo bioassay, using humanized transgenic mice, is useful for measuring antiandrogens, and is a means to a more relevant bioas-say relating to actual human exposure. |
| Databáze: | OpenAIRE |
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