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.
Amitava Mukherjee  1 ,  Michael W Epperly  1 ,  Renee Fisher  1 ,  Donna Shields  1 ,  Wen Hou  1 ,  Arjun Pennathur  2 ,  James Luketich  2 ,  Hong Wang  3 ,  Joel S Greenberger  4
Affiliations
  • 1. Department Radiation Oncology, UPMC-Hillman Cancer Center, Pittsburgh, PA, U.S.A.
  • 2. Department Thoracic Surgery, UPMC-Presbyterian Hospital, Pittsburgh, PA, U.S.A.
  • 3. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, U.S.A.
  • 4. Department Radiation Oncology, UPMC-Hillman Cancer Center, UPMC Cancer Pavilion, Pittsburgh, PA, U.S.A. [email protected].
PMID: 36881075 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.
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