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Inter-validation of the in vitro transactivation assay to test (anti)androgenic potential compounds by using 22Rv1/ mouse mammary tumor virus cells

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한국발생생물학회 (The Korea Society Of Developmental Biology)
초록

Endocrine disruptors are exogenous chemicals that their endocrine disrupting effects mediated by androgenic signaling plays crucial roles in the control of development and several androgen-related diseases. However, there are no authorized in vitro screening and testing methods to evaluation of (anti-)androgenic activity. To find out a better in vitro cell line model, we have previously reported that 22Rv1 cells, a human prostate cancer cells contained functional Androgen Receptor (AR), might be an appropriate model for the evaluation of (anti-)androgenic endocrine disruptors. Based on this result, we developed a stable 22Rv1/mouse mammary tumor virus (MMTV) cell line to test AR-mediated transcriptional activation (TA). Using 22Rv1/MMTV cells, we established the test protocol and optimized the testing condition for AR-TA assay. In this study, we performed the inter-validation assay by four different laboratories to evaluate the 20 coded chemicals which were selected from the ICCVAM list (ICCVAM, 2003) or academic articles that exhibited exact (anti-) androgenic activity. The statistical analysis of the results of the inter-laboratory validation study revealed that there was reproducibility between the four participating laboratories. In conclusion, 22Rv1/MMTV AR-TA assay might be a quick and relatively inexpensive method, which can be used to screen large numbers of chemicals for their potential to activate or inhibit AR-mediated gene transcription. Furthermore, it will provide mechanistic data relevant to understanding adverse reactions observed in intact organisms.

저자
  • Hee-Seok Lee(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • Eun-Jung Park(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • Songyi Han(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • Gyeong-Yong Oh(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • Min-Hee Kim(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • Kwang-Soo Lee(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • Myung-Sil Hwang(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • Guiim Moon(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)
  • In-Gyun Hwang(Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation)