Related Experiment Videos
Inhibition of natural killer cell activity in mice treated with tobacco specific carcinogen NNK
1Department of Microbiology and Immunology, University of Kentucky, Lexington, USA.
Abstract:
Among the different chemicals present in tobacco and tobacco smoke, 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is the most potent carcinogen. In the present study the immunosuppressive effect of NNK was investigated in laboratory animals by analyzing the antitumor immune responses. Mice of B6C3F1 strain were treated with different doses of NNK by IP and assayed for natural killer cell activity by the lysis of 51Cr-labeled YAC-1 lymphoma cells. The control mice received physiological saline. The results showed a significant inhibition of natural killer cell activity in the spleen cells of mice treated with 100 or 250 mg/kg NNK. In contrast to the high-dose NNK group, treatment of mice with lower doses of NNK like 10 or 50 mg/kg had no significant effect on the natural killer cell activity. In addition to spleen, the natural killer cell activity was also suppressed in the hilar lymph nodes and lung cells of NNK-treated mice. The clearance of 125I labeled YAC-1 tumor cells was also reduced from the lungs of mice injected with NNK. Further, the metastatic potential of B16F10 melanoma cells was significantly higher, as evidenced by the increased lung tumor nodules in the high-dose NNK-treated mice. The decreased antitumor immune response in the carcinogen-treated mice was not due to a decrease of NK cells, because flow cytometric analysis indicated no change in the frequency of NK 1.1+ cells between control and treated animals. However, there was an increased plasma cortisone levels in the carcinogen-treated mice compared to control animals. Injection of mice with poly I:C or interleukin-12 was able to restore natural killer cell activity in the tobacco carcinogen-treated mice.
Insights
Tobacco carcinogen 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) suppresses antitumor immunity by inhibiting natural killer (NK) cell activity. This immunosuppression, linked to increased cortisone, enhances tumor metastasis but can be reversed with immune stimulants.
Area of Science:
- Immunology
- Toxicology
- Cancer Research
Background:
- Tobacco smoke contains 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen.
- NNK's impact on antitumor immune responses, particularly natural killer (NK) cell activity, requires detailed investigation.
- Understanding NNK's immunosuppressive mechanisms is crucial for cancer prevention and treatment strategies.
Purpose of the Study:
- To investigate the immunosuppressive effects of NNK on antitumor immunity in laboratory animals.
- To analyze the impact of NNK on NK cell activity and its correlation with tumor metastasis.
- To explore potential mechanisms behind NNK-induced immunosuppression and evaluate restoration strategies.
Main Methods:
- Mice were treated with varying doses of NNK via intraperitoneal injection.
- NK cell activity was assessed using 51Cr-labeled YAC-1 lymphoma cells.
- Tumor cell clearance, metastatic potential, NK cell frequency (flow cytometry), and plasma cortisone levels were analyzed.
Main Results:
- High doses of NNK (100-250 mg/kg) significantly inhibited NK cell activity in spleen, lymph nodes, and lungs.
- NNK treatment reduced tumor cell clearance and increased lung metastasis of B16F10 melanoma cells.
- Increased plasma cortisone levels were observed, while NK cell frequency remained unchanged, suggesting functional impairment rather than depletion.
Conclusions:
- NNK effectively suppresses antitumor immunity by impairing NK cell function, leading to increased tumor metastasis.
- Elevated cortisone levels may contribute to NNK-induced immunosuppression.
- Immune restoration was achieved using poly I:C or interleukin-12, highlighting potential therapeutic interventions.