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Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line
Author(s) -
Ding Ling,
Murphy Margaret B.,
He Yuhe,
Xu Yan,
Yeung Leo W.Y.,
Wang Jingxian,
Zhou Bingsheng,
Lam Paul K.S.,
Wu Rudolf S.S.,
Giesy John P.
Publication year - 2007
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1897/06-388r1.1
Subject(s) - adrenocortical carcinoma , polybrominated diphenyl ethers , steroidogenic acute regulatory protein , chemistry , cytochrome p450 , endocrine system , steroid biosynthesis , brominated flame retardant , aromatase , tetrabromobisphenol a , viability assay , carcinogen , gene expression , gene , medicine , biology , enzyme , endocrinology , hormone , biochemistry , pollutant , steroid , cell , fire retardant , genetics , organic chemistry , cancer , breast cancer
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 ), 3β‐hydroxysteroid dehydrogenase ( 3 β HSD2 ), 17β‐hydroxysteroid dehydrogenase (17β HSD1 and 17β HSD4 ), 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, 3β HSD2 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.