Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line.

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Ding L, Murphy MB, He Y, Xu Y, Yeung LW, Wang J, Zhou B, Lam PK, Wu RS, Giesy JP

Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line.

Environ Toxicol Chem. 2007 Apr;26(4):764-72.

PubMed ID
17447562 [ View in PubMed
]
Abstract

Brominated flame retardants (BFRs) and brominated dioxins are emerging persistent organic pollutants that are ubiquitous in the environment and can be accumulated by wildlife and humans. These chemicals can disturb endocrine function. Recent studies have demonstrated that one of the mechanisms of endocrine disruption by chemicals is modulation of steroidogenic gene expression or enzyme activities. In this study, an in vitro assay based on the H295R human adrenocortical carcinoma cell line, which possesses most key genes or enzymes involved in steroidogenesis, was used to examine the effects of five bromophenols, two polybrominated biphenyls (PBBs 77 and 169), 2,3,7,8-tetrabromodibenzo-p-dioxin, and 2,3,7,8-tetrabromodibenzofuran on the expression of 10 key steroidogenic genes. The H295R cells were exposed to various BFR concentrations for 48 h, and the expression of specific genes--cytochrome P450 (CYP11A, CYP11B2, CYP17, CYP19, and CYP21), beta-hydroxysteroid dehydrogenase (3betaHSD2), 17beta-hydroxysteroid dehydrogenase (17betaHSD1 and 17betaHSD4), steroidogenic acute regulatory protein (StAR), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR)--was quantitatively measured using real-time polymerase chain reaction. Cell viability was not affected at the doses tested. Most of the genes were either up- or down-regulated, to some extent, by BFR exposure. Among the genes tested, 3betaHSD2 was the most markedly up-regulated, with a range of magnitude from 1.6- to 20-fold. The results demonstrate that bromophenol, bromobiphenyls, and bromodibenzo-p-dioxin/furan are able to modulate steroidogenic gene expression, which may lead to endocrine disruption.

DrugBank Data that Cites this Article

Pharmaco-transcriptomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
o-BromophenolExperimentalCYP11A11583
upregulated		2-bromophenol results in increased expression of CYP11A1 mRNA15q24.1
o-BromophenolExperimentalCYP17A11586
upregulated		2-bromophenol results in increased expression of CYP17A1 mRNA10q24.32
o-BromophenolExperimentalCYP19A11588
upregulated		2-bromophenol results in increased expression of CYP19A1 mRNA15q21.2
o-BromophenolExperimentalHSD17B13292
upregulated		2-bromophenol results in increased expression of HSD17B1 mRNA17q21.2
o-BromophenolExperimentalHSD17B43295
upregulated		2-bromophenol results in increased expression of HSD17B4 mRNA5q23.1
o-BromophenolExperimentalHSD3B23284
upregulated		2-bromophenol results in increased expression of HSD3B2 mRNA1p12
o-BromophenolExperimentalSTAR6770
upregulated		2-bromophenol results in increased expression of STAR mRNA8p11.23
PentabromophenolExperimentalCYP11A11583
upregulated		pentabromophenol results in increased expression of CYP11A1 mRNA15q24.1
PentabromophenolExperimentalCYP11B21585
upregulated		pentabromophenol results in increased expression of CYP11B2 mRNA8q24.3
PentabromophenolExperimentalCYP17A11586
upregulated		pentabromophenol results in increased expression of CYP17A1 mRNA10q24.32
PentabromophenolExperimentalCYP19A11588
upregulated		pentabromophenol results in increased expression of CYP19A1 mRNA15q21.2
PentabromophenolExperimentalCYP21A21589
upregulated		pentabromophenol results in increased expression of CYP21A2 mRNA6p21.33
PentabromophenolExperimentalHMGCR3156
downregulated		pentabromophenol results in decreased expression of HMGCR mRNA5q13.3
PentabromophenolExperimentalHMGCR3156
upregulated		pentabromophenol results in increased expression of HMGCR mRNA5q13.3
PentabromophenolExperimentalHSD17B13292
upregulated		pentabromophenol results in increased expression of HSD17B1 mRNA17q21.2
PentabromophenolExperimentalHSD3B23284
upregulated		pentabromophenol results in increased expression of HSD3B2 mRNA1p12