Liquid Crystal Monomers and Their Mixtures Alter Nuclear Receptor Signaling and Promote Adipogenesis In Vitro

脂肪生成 体外 化学 毒性 甘油三酯 新陈代谢 体内 荧光素酶 单体 体外毒理学 生物化学 核受体 HEK 293细胞 细胞生物学 报告基因 液晶 受体 脂质代谢 内分泌学 内科学 人类健康 污染 药理学 生物物理学 小RNA 生物 代谢途径
作者
Samantha Heldman,Kristin M. Eccles,Christopher D. Kassotis
出处
期刊:Endocrinology [Oxford University Press]
卷期号:166 (11) 被引量:1
标识
DOI:10.1210/endocr/bqaf143
摘要

Liquid crystal monomers (LCMs) are ubiquitous environmental contaminants released from electronic devices' liquid crystal display (LCD) panels, which have led to the contamination of food, breast milk, and serum. As the toxicity of individual LCMs, not to mention their myriad mixtures, is currently very poorly characterized, there is a crucial need for investigations into the health hazards posed by exposure. In this study, 10 nonfluorinated (NF) and fluorinated (F) LCMs and 3 fluorination-based LCM mixtures were screened for metabolism and endocrine-disrupting potential in vitro at exposure-relevant concentrations using adipogenesis assays and luciferase reporter gene assays. Both NF-LCMs, F-LCMs, and their mixtures were found to alter the transcriptional activity of one or more nuclear receptors. Notably, 6 LCMs and all LCM mixtures were able to antagonize the progesterone receptor, with several displaying non-monotonic concentration-response curves. Multiple LCMs and their mixtures also increased triglyceride accumulation in murine preadipocytes and human mesenchymal stem cells in a concentration-dependent manner. The concentration addition principle underestimated the adipogenic potencies of LCM mixtures when compared with those derived from benchmark concentration analyses of empirical adipogenesis assay results, suggesting synergistic interactions. While no mechanistic pattern emerged between the bioactivities, results confirmed the metabolism and endocrine-disrupting potential of both NF-LCMs, F-LCMs, and their mixtures. This emphasizes the need to further investigate the metabolic and reproductive health impacts of LCM exposure in vivo, as well as the necessity of exploring alternative models to predict the toxicity of LCM mixtures.
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