Estrogen receptor/androgen receptor transcriptional activation of benzophenone derivatives and integrated approaches to testing and assessment (IATA) for estrogenic effects.

Autor: Lee H; College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea., Park J; College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea., Ortiz DM; College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea., Park K; College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea. Electronic address: kspark@dongduk.ac.kr.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2024 Oct; Vol. 100, pp. 105914. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1016/j.tiv.2024.105914
Abstrakt: Estrogen receptor (ER) and androgen receptor (AR) transactivation assays for the benzophenone compounds (BPs) were performed using hERα-HeLa-9903 cells for ER and MMTV/22Rv1_GR-KO cells for AR. Results showed that some BPs, such as BP-1, BP-2, 4OH-BP, 4DHB, and 4-MBP, showed agonistic activity on ER with a higher RPCmax than 1 nM 17-β estradiol. The other BPs (BP, BP-3, BP-6, BP-7, and BP-8) showed low RPCmax in accordance with the OECD Test guideline (TG) 455 criteria, with BP-4 as the only ER-negative. However, the potency of the BPs was at least 1000 times less than the reference chemical, 17-β-estradiol. None of the BPs exhibited agonistic activity on AR except BP-2 which showed a small increase in activity. For further evaluation of the estrogenic effect of BPs based on the integrated approaches to testing and assessment (IATA) approach, existing data on ER binding, steroidogenesis, MCF-7 cell proliferation, and in vivo uterotrophic assays were collected and evaluated. There seemed to be a close association between the in vitro data on BPs, especially ER transcriptional activity, and the in vivo results of increased uterine weight. This case study implied that integrated approaches using in vitro data can be a useful tool for the prediction of in vivo data for estrogenic effects, without the need for additional animal toxicity tests.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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