Canton, Rocío F; Sanderson, J. Thomas 
ORCID: https://orcid.org/0000-0002-3190-2811; Letcher, Robert J.; Bergman, Ake et van den Berg, Martin
(2005).
Inhibition and induction of aromatase (CYP19) activity by brominated flame retardants in H295R human adrenocortical carcinoma cells
Toxicological Sciences
, vol. 88
, nº 2.
pp. 447-455.
DOI: 10.1093/toxsci/kfi325.
Résumé
Brominated flame retardants (BFRs) are persistent and ubiquitous chemicals in the environment, and they are found at increasing levels in tissues of wildlife and humans. Previous in vitro studies with the BFR class of polybrominated diphenyl ethers (BDEs) have shown endocrine-disrupting properties. Our study assessed the potential effects of nineteen BDEs, five hydroxylated BDEs (OH-BDEs), one methoxylated BDE (CH(3)O-BDE), tetrabromobisphenol-A (TBBPA), its dibromopropane ether derivative (TBBPA-DBPE), and the brominated phenols/anisols 2,4,6-tribromophenol (TBP), 4-bromophenol (4BP) and 2,4,6-tribromoanisole (TBA) on the catalytic activity of the steroidogenic enzyme aromatase (CYP19) in H295R human adrenocortical carcinoma cells. Effects were studied in the concentration range from 0.5 to 7.5 microM; exposures were for 24 h. Both 6-OH-BDE47 and 6-OH-BDE99 showed an inhibitory effect on aromatase activity at concentrations >2.5 microM and >5 microM, respectively. However, 6-OH-BDE47 also caused a statistically significant increase in cytotoxicity (based on mitochondrial MTT reduction and lactate dehydrogenase-leakage [LDH]) at concentrations >2.5 microM that could explain in part the apparent inhibitory effect on aromatase activity. Compared to 6-OH-BDE47, the methoxy analog (6-CH(3)O-BDE47) did not elicit a cytotoxic effect, whereas significant inhibition of aromatase remained. TBP caused a concentration-dependent induction of aromatase activity between 0.5 and 7.5 microM (with a maximum of 3.8-fold induction at 7.5 microM). This induction was not observed when a OH- group replaced the CH(3)O- group or when bromine atoms adjacent to this OH- group were absent. These in vitro results provide a basis for studies of more detailed structure-activity relationships between these brominated compounds and the modulation of aromatase activity.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | brominated flame retardants (BFRs); BDEs; OH-PBDEs; CH3O-PBDEs; aromatase (CYP19); human adrenocortical (H295R) cell line |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 01 nov. 2024 14:05 |
| Dernière modification: | 01 nov. 2024 14:05 |
| URI: | https://espace.inrs.ca/id/eprint/14461 |
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