Organochlorine pesticides induce inflammation, ROS production, and DNA damage in human epithelial ovary cells: An in vitro study

Chemosphere. 2020 May:246:125691. doi: 10.1016/j.chemosphere.2019.125691. Epub 2019 Dec 19.

Abstract

Although the etiology of ovarian cancer is not clear, certain factors are implicated in this disease, such as ovulation, gonadotropic and steroid hormones, growth factors, cytokines, environmental agents, etc. Epidemiological studies have proven environmental exposure to pesticides with an increased risk of Epithelial Ovarian Cancer (EOC); however, the molecular mechanism underlying the carcinogenic effects of pesticides in human ovary remains poorly understood. The present study aimed to study the pro-inflammatory response of organochlorine pesticides (OCPs) namely β-hexachlorocyclohexane (β-HCH), dichlorodiphenyldichloroethylene (DDE) and Dieldrin following exposure to human ovary surface epithelial cells (HOSE) for risk prediction of epithelial ovarian cancer. We found high level of Reactive oxygen species (ROS) production and DNA damage along with up-regulation of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, nuclear factor kappa B (NF-kB) and cyclooxygenase (COX)-2 expression in OCPs treated HOSE cells compared to control (DMSO). The result of the present study suggests that β-HCH, DDE, and Dieldrin exposure induce ROS and pro-inflammatory response as well as DNA damage in HOSE cells. These various results show that OCPs may account for the neoplastic transformation of HOSE cells in the ovary.

Keywords: Cytokine; DNA damage; Epithelial ovary cancer; Human ovary surface epithelial cell; Inflammation; Organochlorine pesticides; ROS.

MeSH terms

  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • DNA Damage
  • Dichlorodiphenyl Dichloroethylene / metabolism
  • Environmental Exposure
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Hydrocarbons, Chlorinated / analysis
  • Hydrocarbons, Chlorinated / toxicity*
  • Inflammation / metabolism
  • Ovarian Neoplasms / metabolism
  • Pesticides / analysis
  • Pesticides / toxicity*
  • Reactive Oxygen Species / metabolism*
  • Toxicity Tests
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Hydrocarbons, Chlorinated
  • Pesticides
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Dichlorodiphenyl Dichloroethylene
  • Cyclooxygenase 2