Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line.
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.
Ding
Ling
L
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China.
Murphy
Margaret B
MB
He
Yuhe
Y
Xu
Yan
Y
Yeung
Leo W Y
LW
Wang
Jingxian
J
Zhou
Bingsheng
B
Lam
Paul K S
PK
Wu
Rudolf S S
RS
Giesy
John P
JP
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005411:Flame Retardants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
D017931:DNA Primers; D018076:DNA, Complementary; D004147:Dioxins; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D003577:Cytochrome P-450 Enzyme System; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D006903:Hydroxymethylglutaryl CoA Reductases