β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Int J Mol Sci. 2021 May 29;22(11):5834. doi: 10.3390/ijms22115834.

Abstract

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent.

Keywords: carcinogenesis; organochlorine pollutants (OCPs); signal transduction; β hexachlorocyclohexane (β-HCH).

MeSH terms

  • Apoptosis / drug effects
  • Biomarkers
  • Biomarkers, Tumor
  • Carcinogens / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation
  • Cell Transformation, Neoplastic / chemically induced*
  • Cells, Cultured
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Gene Expression
  • Hexachlorocyclohexane / adverse effects
  • Hexachlorocyclohexane / pharmacology*
  • Humans
  • Reactive Oxygen Species / metabolism
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology*
  • Signal Transduction / drug effects

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Carcinogens
  • Reactive Oxygen Species
  • Hexachlorocyclohexane
  • beta-hexachlorocyclohexane