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

致癌物 4-硝基喹啉氧化物 (4-NQO) 诱导食管细胞中的抑癌素-M (OSM)

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作者:Amitava Mukherjee, Michael W Epperly, Renee Fisher, Donna Shields, Wen Hou, Arjun Pennathur, James Luketich, Hong Wang, Joel S Greenberger

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

Conclusion

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

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.

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