Effects of environmental carcinogen benzo(a)pyrene on canine adipose-derived mesenchymal stem cells

Res Vet Sci. 2015 Dec:103:34-43. doi: 10.1016/j.rvsc.2015.09.012. Epub 2015 Sep 14.

Abstract

Dogs and their owners share the same environment and are subjected to similar environmental risk factors for developing breast cancer. Adipose tissue-derived mesenchymal stem cells (ADMSCs) may affect development and progression of breast cancer. In this study, we evaluated the effects of environmental carcinogen benzo(a)pyrene (BaP) on proliferation and differentiation of ADMSCs isolated from dogs. We characterized eight canine ADMSC lines and studied the effects of BaP on cell proliferation and differentiation. BaP did not inhibit cell proliferation of ADMSCs; however, BaP significantly inhibited differentiation potential of ADMSCs into adipocytes. BaP down-regulated AhR protein levels; however, increased its translocation from the cytoplasm to nucleus and suppressed PPARγ expression during adipogenesis. BaP increased the expression of AhR signaling pathway protein, cytochrome P450 (CYP1A1) in ADMSCs. Our data suggest that canine ADMSCs are susceptible to the environmental carcinogen BaP through AhR and PPARγ signaling pathways and may contribute to canine mammary carcinogenesis.

Keywords: Adipogenesis; AhR signaling pathway; Benzo(a)pyrene; Canine; Environmental carcinogenesis; Mesenchymal stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzo(a)pyrene / toxicity*
  • Carcinogens, Environmental / toxicity*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Dogs / metabolism*
  • Environmental Pollutants / toxicity*
  • Gene Expression Regulation / drug effects
  • Mesenchymal Stem Cells / drug effects*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism

Substances

  • Carcinogens, Environmental
  • Environmental Pollutants
  • PPAR gamma
  • Receptors, Aryl Hydrocarbon
  • Benzo(a)pyrene