P138 Lack of estrogenic and anti-estrogenic activity of aromatic amines and their hydroxylated and acetylated metabolites on human breast cancer cells

Linh Chi Bui , CNRS UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Kevin Cariou , CNRS UPR 2301, Gif-sur-Yvette, France
Gautier Moroy , Inserm UMR-S 973, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Jean-Marie Dupret , Sciences du Vivant, CNRS UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Fernando Rodrigues-Lima , Sciences du Vivant, CNRS UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Aromatic amines (AA) are widely present in the environment and account for approximately 12 % of the chemicals that are known or are strongly suspected to be carcinogenic in human. Estrogen receptors (ERs) play an important role in the regulation of proliferation and cell differentiation in response to estrogen (E2), particularly in cancer cells. The purpose of this study was to investigate, in two human breast cancer cell lines (MCF7 and T47D-KbLuc), the potential estrogenic capacity of several AAs, as well as their metabolites, to bind the estrogen receptor (ERs). The parent AAs and their acetylated and/or hydroxylated metabolites were each evaluated using transcriptional reporter assays to measure receptor activation, binding assays to determine ligand-receptor affinity, quantitative real-time PCR of estrogen -responsive target genes and proliferation assay to assess the estrogenic and/or anti-estrogenic activities. In contrast to E2 and BPA, two well-known estrogenic compounds, all tested AAs and metabolites did not produce any estrogenic or anti-estrogenic responses in all assay systems. These data indicate that the carcinogenicity of these AAs is not associated with estrogenic potential.