The H295R system for evaluation of endocrine-disrupting effects

被引:85
作者
Gracia, Tannia [1 ]
Hilscherova, Klara
Jones, Paul D.
Newsted, John L.
Zhang, Xiaowei
Hecker, Markus
Higley, Eric B.
Sanderson, J. T.
Yu, Richard M. K.
Wu, Rudolf S. S.
Giesy, John P.
机构
[1] Michigan State Univ, Dept Zool, Natl Food Safety & Toxicol Ctr 218C, Ctr Integrat Toxicol, E Lansing, MI 48824 USA
[2] ENTRIX Inc, E Lansing, MI 48864 USA
[3] City Univ Hong Kong, Kowloon, Hong Kong, Peoples R China
[4] Univ Quebec, INRS, IAF, Pointe Claire, PQ H9R 1G6, Canada
[5] Univ Saskatchewan, Dept Vet Biomed Sci, Saskatoon, SK, Canada
[6] Univ Saskatchewan, Toxicol Ctr, Saskatoon, SK, Canada
关键词
bioassay; steroidogenesis; screening; endocrine disruptors; mixtures;
D O I
10.1016/j.ecoenv.2006.06.012
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
The present studies were undertaken to evaluate the utility of the H295R system as an in vitro assay to assess the potential of chemicals to modulate steroidogenesis. The effects of four model chemicals on the expression of ten steroidogenic genes and on the production of three steroid hormones were examined. Exposures with individual model chemicals as well as binary mixtures were conducted. Although the responses reflect the known mode of action of the various compounds, the results show that designating a chemical as "specific inducer or inhibitor" is unwise. Not all changes in the mixture exposures could be predicted based on results from individual chemical exposures. Hormone production was not always directly related to gene expression. The H295R system integrates the effects of direct-acting hormone agonists and antagonists as well as chemicals affecting signal transduction pathways for steroid production and provides data on both gene expression and hormone secretion which makes this cell line a valuable tool to examine effects of chemicals on steroidogenesis. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:293 / 305
页数:13
相关论文
共 44 条
  • [1] Overview of a workshop on screening methods for detecting potential (anti-) estrogenic/androgenic chemicals in wildlife
    Ankley, G
    Mihaich, E
    Stahl, R
    Tillitt, D
    Colborn, T
    McMaster, S
    Miller, R
    Bantle, J
    Campbell, P
    Denslow, N
    Dickerson, R
    Folmar, L
    Fry, M
    Giesy, J
    Gray, LE
    Guiney, P
    Hutchinson, T
    Kennedy, S
    Kramer, V
    LeBlanc, G
    Mayes, M
    Nimrod, A
    Patino, R
    Peterson, R
    Purdy, R
    Ringer, R
    Thomas, P
    Touart, L
    Van der Kraak, G
    Zacharewski, T
    [J]. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 1998, 17 (01) : 68 - 87
  • [2] Evolution of 17β-hydroxysteroid dehydrogenases and their role in androgen, estrogen and retinoid action
    Baker, ME
    [J]. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2001, 171 (1-2) : 211 - 215
  • [3] Aminoglutethimide, a steroidogenesis inhibitor, abolishes hormonal induction of ornithine decarboxylase in steroidogenic tissues:: Evidence for its role as cAMP-dependent protein kinase inhibitor
    Bastida, CM
    Tejada, F
    Cremades, A
    Peñafiel, R
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 281 (01) : 244 - 248
  • [4] CYP11A1 stimulates the hydroxylase activity of CYP11B1 in mitochondria of recombinant yeast in vivo and in vitro
    Cauet, G
    Balbuena, D
    Achstetter, T
    Dumas, B
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (14): : 4054 - 4062
  • [5] Forskolin treatment directs steroid production towards the androgen pathway in the NCI-H295R adrenocortical tumour cell line
    Cobb, VJ
    Williams, BC
    Mason, JI
    Walker, SW
    [J]. ENDOCRINE RESEARCH, 1996, 22 (04) : 545 - 550
  • [6] COLBORN T, 1997, OUR STOLEN FUTURE AR, P21
  • [7] DIMATTINA M, 1988, FERTIL STERIL, V49, P62
  • [8] Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus
    Dodds, EC
    Lawson, W
    [J]. PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES, 1938, 125 (839): : 222 - 232
  • [9] GAZDAR AF, 1990, CANCER RES, V50, P5488
  • [10] REGULATION OF THE MEVALONATE PATHWAY
    GOLDSTEIN, JL
    BROWN, MS
    [J]. NATURE, 1990, 343 (6257) : 425 - 430