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Updated: Aug 9, 2025

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Chronic Exposure to Nitric Oxide Induces P53 Mutations and Malignant-like Features in Human Breast Epithelial Cells

Robert Y S Cheng1, Sandra Burkett2, Stefan Ambs3

  • 1Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.

Biomolecules
|February 25, 2023
PubMed

Insights

Chronic nitric oxide (NO) exposure alters breast cells, inducing genomic instability and malignant phenotypes. This study reveals NO

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Nitric oxide (NO) is an endogenous signaling molecule implicated in chronic inflammation and cancer.
  • NO's effects are concentration- and time-dependent, with roles in both protection and DNA damage.
  • Understanding NO's role in carcinogenesis requires investigating its effects on epithelial cells.

Purpose of the Study:

  • To investigate the effects of chronic nitric oxide (NO) exposure on MCF10A breast epithelial cells.
  • To define changes in cellular morphology, genomic stability, gene expression, and cell phenotypes.
  • To elucidate the role of NO in breast carcinogenesis.

Main Methods:

  • MCF10A human breast epithelial cells were treated with varying doses of the NO donor DETANO for three weeks.
  • Genomic modifications, gene expression (quantitative real-time PCR), cell morphology, motility, and colony formation were analyzed.
  • TP53 and KRAS target genes were examined for distinct genomic modifications.

Main Results:

  • Chronic NO exposure induced distinct genomic modifications in TP53 and KRAS target genes.
  • Increased expression of cancer stem cell (CSC) marker CD44 was observed after exposure to 300 microM DETANO.
  • Enhanced cell motility, proliferation in serum-free media, and disorganized colony formation in soft agar were noted at 100 microM NO.

Conclusions:

  • Chronic NO exposure alters breast epithelial cell phenotypes, conferring malignant characteristics.
  • NO-induced changes include genomic instability and altered cell behavior, suggesting a role in carcinogenesis.
  • These findings highlight the complex role of NO in cancer development.
Keywords:
TP53breast cancermutationnitric oxide

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