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An in vivo bioassay for detecting antiandrogens using humanized transgenic mice coexpressing the tetracycline-controlled transactivator and human CYP1B1 gene
- An in vivo bioassay for detecting antiandrogens using humanized transgenic mice coexpressing the tetracycline-controlled transactivator and human CYP1B1 gene
- Hwang D.Y.; Cho J.S.; Oh J.H.; Shim S.B.; Jee S.W.; Lee S.H.; Seo S.J.; Kang H.G.; Sheen Y.Y.; Kim Y.K.
- Ewha Authors
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- International Journal of Toxicology
- International Journal of Toxicology vol. 24, no. 3, pp. 157 - 164
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- 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 hC P1B1 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 bioassay relating to actual human exposure. Copyright © American College of Toxicology.
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