Related Experiment Video
Updated: Jul 11, 2025
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
4-nitroquinoline 1-oxide induces immune cells death to onset early immunosuppression during oral squamous cell
Satya Ranjan Sahu1,2, Shweta Thakur1, Doureradjou Peroumal1
1Laboratory of Genomic Instability and Diseases, Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, India.
Abstract:
4-Nitroquinoline N-oxide (4-NQO) and its derivatives react with genomic DNA to form stable quinolone monoadducts, which are highly mutagenic and genotoxic. While the chronic high-dose exposure of epithelial cells to a carcinogen such as 4-NQO leads to tumor development, its effect on other cells has not been explored yet. Since the immunosuppression due to aberrant immunological profile is recognized as a significant cause in tumors, here we determine the interaction between 4-NQO and immune cells both in vivo and in vitro, and its effect on oral squamous cell carcinoma (OSCC) progression in a murine model. Immune cell profiling of the spleen and peripheral blood revealed a significant decrease in the B-cell population in 4-NQO-exposed mice than the untreated group. Additionally, γδ T and CD5+ B lymphocyte populations decreased at both pre- and post-cancerous stages of OSCC. These results suggested that 4-NQO induced tumor transition from pre-malignant lesions to OSCC by altering certain immune cells systemically. Next, to establish the effect of 4-NQO on immune cells, human B- and T-cell lines were subjected to 4-NQO; the reduction in cell viability, increase in DNA damage response marker, and induction of apoptosis were more pronounced in B than T cells. Altogether, our results indicated that in addition to the genotoxicity of oral epithelial cells, 4-NQO potentiates long-range effects on specific immune cells to induce cell death to cause very-early immunosuppressive response during oral carcinogenesis, and thus immunosuppression and tumor development are coevolved.
Insights
4-Nitroquinoline N-oxide (4-NQO) causes DNA damage and tumor development. This study shows 4-NQO also harms immune cells, specifically B cells, leading to immunosuppression and oral cancer progression.
Area of Science:
- Immunology
- Toxicology
- Oncology
Background:
- 4-Nitroquinoline N-oxide (4-NQO) is a known genotoxic carcinogen causing DNA damage.
- While its effects on epithelial cells are studied, its impact on immune cells and cancer progression remains less explored.
- Immunosuppression is increasingly recognized as a factor in tumor development.
Purpose of the Study:
- To investigate the interaction between 4-NQO and immune cells.
- To determine the effect of 4-NQO on oral squamous cell carcinoma (OSCC) progression.
- To elucidate the role of 4-NQO-induced immunosuppression in oral carcinogenesis.
Main Methods:
- In vivo studies using a murine model exposed to 4-NQO.
- In vitro experiments with human B- and T-cell lines treated with 4-NQO.
- Immune cell profiling of spleen and peripheral blood.
- Assessment of cell viability, DNA damage, and apoptosis.
Main Results:
- 4-NQO exposure led to a significant decrease in B-cell populations in mice.
- γδ T and CD5+ B lymphocyte populations were reduced in pre- and post-cancerous OSCC stages.
- In vitro, 4-NQO induced greater cell death, DNA damage, and apoptosis in B cells compared to T cells.
- 4-NQO demonstrated systemic effects on immune cells, contributing to immunosuppression.
Conclusions:
- 4-NQO's genotoxicity extends to specific immune cells, particularly B cells.
- The compound induces early immunosuppression by promoting immune cell death.
- 4-NQO-induced immunosuppression and oral tumor development are interconnected processes.
