Heneweer, Marjoke; van den Berg, Martin; de Geest, Maarten C.; de Jong, Paul C.; Bergman, Ake et Sanderson, J. Thomas 
ORCID: https://orcid.org/0000-0002-3190-2811
(2005).
Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts
Toxicology and Applied Pharmacology
, vol. 202
, nº 1.
pp. 50-58.
DOI: 10.1016/j.taap.2004.06.006.
Résumé
In this study, the effects on catalytic activity and mRNA levels of aromatase in primary human mammary fibroblasts were evaluated after exposure to promoter-specific modulators of aromatase expression and methyl sulfonyl polychlorinated biphenyl metabolites (MeSO(2)-PCBs). A method for fibroblast isolation from primary breast tissue was developed and optimized, and aromatase activity and promoter-specific mRNA levels were assessed in these cells after exposure to test compounds. A 24-h exposure of fibroblasts to dexamethasone (DEX) (1-100 nM) increased aromatase activity to a maximum of 313-fold. DEX also elevated promoter I.4-specific RNA levels. A 24-h exposure of fibroblasts to 3-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-91, or 4-MeSO(2)-PCB-149 (0.1-10 microM) resulted in a concentration-dependent decrease of aromatase activity. Exposure of fibroblasts to MeSO(2)-PCBs just for the limited duration (6 h) of the catalytic assay caused a concentration-dependent inhibition of aromatase enzyme activity. mRNA levels were not altered by a 24-h MeSO(2)-PCB exposure nor was cytotoxicity observed. In aromatase-expressing human adrenocortical carcinoma H295R cells, a 24-h exposure to 3-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-132, 4-MeSO(2)-PCB-91, or 4-MeSO(2)-PCB-149 (0.1-10 microM) also resulted in a concentration-dependent decrease of aromatase activity. Additionally, there were no changes in aromatase mRNA levels after 24-h exposure of H295R cells to MeSO(2)-PCBs. We conclude that in primary human mammary fibroblasts as well as in H295R cells, aromatase inhibition by MeSO(2)-PCBs is likely to be due to catalytic inhibition.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Aromatase; PCB metabolite; Primary fibroblasts; Human; H295R; Mammary; CYP19; Promoter I.4 |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 01 nov. 2024 20:40 |
| Dernière modification: | 01 nov. 2024 20:40 |
| URI: | https://espace.inrs.ca/id/eprint/14755 |
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