Effects of neonicotinoids on promoter-specific expression and activity of aromatase (CYP19) in human adrenocortical carcinoma (H295R) and primary umbilical vein endothelial (HUVEC) cells

Élyse Caron-Beaudoin, Michael S. Denison, J. Thomas Sanderson

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The enzyme aromatase (CYP19; cytochrome P450 19) in humans undergoes highly tissue- and promoter-specific regulation. In hormone-dependent breast cancer, aromatase is over-expressed via several normally inactive promoters (PII, I.3, I.7). Aromatase biosynthesizes estrogens, which stimulate breast cancer cell proliferation. The placenta produces estrogens required for healthy pregnancy and the major placental CYP19 promoter is I.1. Exposure to certain pesticides, such as atrazine, is associated with increased CYP19 expression, but little is known about the effects of neonicotinoid insecticides on CYP19. We developed sensitive and robust RT-qPCR methods to detect the promoter-specific expression of CYP19 in human adrenocortical carcinoma (H295R) and primary umbilical vein endothelial (HUVEC) cells, and determined the potential promoter-specific disruption of CYP19 expression by atrazine and the commonly used neonicotinoids imidacloprid, thiacloprid, and thiamethoxam. In H295R cells, atrazine concentration-dependently increased PII- and I.3-mediated CYP19 expression and aromatase catalytic activity. Thiacloprid and thiamethoxam induced PII- and I.3-mediated CYP19 expression and aromatase activity at relatively low concentrations (0.1-1.0 μM), exhibiting non-monotonic concentration-response curves with a decline in gene induction and catalytic activity at higher concentrations. In HUVEC cells, atrazine slightly induced overall (promoter-indistinct) CYP19 expression (30 μM) and aromatase activity (≥ 3 μM), without increasing I.1 promoter activity. None of the neonicotinoids increased CYP19 expression or aromatase activity in HUVEC cells. Considering the importance of promoter-specific (over)expression of CYP19 in disease (breast cancer) or during sensitive developmental periods (pregnancy), our newly developed RT-qPCR methods will be helpful tools in assessing the risk that neonicotinoids and other chemicals may pose to exposed women.

Original languageEnglish (US)
Article numberkfv220
Pages (from-to)134-144
Number of pages11
JournalToxicological Sciences
Volume149
Issue number1
DOIs
StatePublished - Jan 1 2016

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Adrenocortical Carcinoma
Umbilical Veins
Aromatase
Endothelial cells
Human Umbilical Vein Endothelial Cells
Endothelial Cells
Atrazine
Breast Neoplasms
Estrogens
Catalyst activity
Pregnancy

Keywords

  • aromatase
  • CYP19
  • H295R
  • HUVEC
  • Neonicotinoids
  • promoter-specific

ASJC Scopus subject areas

  • Toxicology

Cite this

Effects of neonicotinoids on promoter-specific expression and activity of aromatase (CYP19) in human adrenocortical carcinoma (H295R) and primary umbilical vein endothelial (HUVEC) cells. / Caron-Beaudoin, Élyse; Denison, Michael S.; Sanderson, J. Thomas.

In: Toxicological Sciences, Vol. 149, No. 1, kfv220, 01.01.2016, p. 134-144.

Research output: Contribution to journalArticle

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