Carcinogen 4-Nitroquinoline Oxide (4-NQO) Induces Oncostatin-M (OSM) in Esophageal Cells

In Vivo. 2023 Mar-Apr;37(2):506-518. doi: 10.21873/invivo.13108.

Abstract

Background/aim: The earliest cellular and molecular biologic changes in the esophagus that lead to esophageal cancer were evaluated in a mouse model. We correlated numbers of senescent cells with the levels of expression of potentially carcinogenic genes in sorted side population (SP) cells containing esophageal stem cells and non-stem cells in the non-side population cells in the 4-nitroquinolone oxide (NQO)-treated esophagus.

Materials and methods: We compared stem cells with non-stem cells from the esophagus of mice treated with the chemical carcinogen 4-NQO (100 μg/ml) in drinking water. We also compared gene expression in human esophagus samples treated with 4-NQO (100 μg/ml media) to non-treated samples. We separated and quantitated the relative levels of expression of RNA using RNAseq analysis. We identified senescent cells by luciferase imaging of p16+/LUC mice and senescent cells in excised esophagus from tdTOMp16+ mice.

Results: A significant increase in the levels of RNA for oncostatin-M was found in senescent cells of the esophagus from 4-NQO-treated mice and human esophagus in vitro.

Conclusion: Induction of OSM in chemically-induced esophageal cancer in mice correlates with the appearance of senescent cells.

Keywords: 4-nitroquinoline oxide; Esophageal cancer; esophageal stem cell; stem cell sorting.

MeSH terms

  • Animals
  • Carcinogens
  • Esophageal Neoplasms* / chemically induced
  • Esophageal Neoplasms* / genetics
  • Humans
  • Mice
  • Mutagens
  • Nitroquinolines*
  • Oncostatin M
  • Oxides
  • RNA

Substances

  • Carcinogens
  • Oxides
  • Mutagens
  • Nitroquinolines
  • RNA
  • OSM protein, human
  • Oncostatin M