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Reduction of daily-use parabens and phthalates reverses accumulation of cancer-associated phenotypes within disease-free breast tissue of study subjects.
Dairkee, Shanaz H; Moore, Dan H; Luciani, M Gloria; Anderle, Nicole; Gerona, Roy; Ky, Karina; Torres, Samantha M; Marshall, Polly V; Goodson Iii, William H.
Afiliação
  • Dairkee SH; California Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA. Electronic address: Shahnaz.Dairkee@sutterhealth.org.
  • Moore DH; California Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA.
  • Luciani MG; California Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA.
  • Anderle N; California Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA.
  • Gerona R; Department of OB/Gyn and Reproductive Sciences, University of California, San Francisco, CA, 94115, USA.
  • Ky K; Department of OB/Gyn and Reproductive Sciences, University of California, San Francisco, CA, 94115, USA.
  • Torres SM; Breast Cancer Over Time, San Francisco, CA, 94110, USA.
  • Marshall PV; Breast Cancer Over Time, San Francisco, CA, 94110, USA.
  • Goodson Iii WH; California Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA.
Chemosphere ; 322: 138014, 2023 May.
Article em En | MEDLINE | ID: mdl-36746253
Estrogenic overstimulation is carcinogenic to the human breast. Personal care products (PCPs) commonly contain xenoestrogens (XE), such as parabens and phthalates. Here, we identified the adverse effects of persistent exposure to such PCPs directly within human estrogen responsive breast tissue of subjects enrolled in a regimen of reduced XE use (REDUXE). Pre- and post-intervention fine needle aspirates (FNAs) of the breast were collected from healthy volunteers who discontinued the use of paraben and phthalate containing PCPs over a 28 d period. Based on high-dimensional gene expression data of matched FNA pairs of study subjects, we demonstrate a striking reversal of cancer-associated phenotypes, including the PI3K-AKT/mTOR pathway, autophagy, and apoptotic signaling networks within breast cells of REDUXE compliant subjects. These, and other altered phenotypes were detected together with a significant reduction in urinary parabens and phthalate metabolites. Moreover, in vitro treatment of paired FNAs with 17ß-estradiol (E2), displayed a 'normalizing' impact of REDUXE on gene expression within known E2-modulated pathways, and on functional endpoints, including estrogen receptor alpha: beta ratio, and S-phase fraction of the cell cycle. In a paradigm shifting approach facilitated by community-based participatory research, REDUXE reveals unfavorable consequences from exposure to XEs from daily-use PCPs. Our findings illustrate the potential for REDUXE to suppress pro-carcinogenic phenotypes at the cellular level towards the goal of breast cancer prevention.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Ftálicos / Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Chemosphere Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos Ftálicos / Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Chemosphere Ano de publicação: 2023 Tipo de documento: Article