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Short term toxicity of nitrous oxide on the immune, hemopoietic, and endocrine systems in CD-1 mice
C E Healy1, D B Drown, R P Sharma
1Department of Biology, Utah State University, Logan 84322-5305.
Abstract:
Occupational exposures to subanesthetic levels of N2O have been documented to result in suppressed proliferative cell activities. Male CD-1 mice were exposed to 0, 50, 500, and 5000 ppm of N2O for 6 hr/day, 5 days/week for 2 or 13 weeks. Tritiated-thymidine ([3H]-TdR) uptake was measured in CD-1 splenic lymphocytes cultured with and without mitogens and in a mixed lymphocyte culture (MLC). Antibody-mediated immunocompetency was determined for sheep red blood cell (SRBC)-sensitized animals by plaque forming cell (PFC) assay and serum anti-SRBC antibody (Ab) titer. Deoxyuridine suppression tests (dUrdST) were performed on bone marrow cells. There was significantly decreased splenic lymphocyte uptake of [3H]-TdR by cells cultured with mitogenic substances and in MLC following 2-week exposures to 5000 ppm. After 13-week exposures the animals' splenic lymphocytes showed increased [3H]-TdR uptake following high N2O dosing in both the mitogen-induced blastogenesis and MLC assays. Compared to control animals, the 5000 ppm exposure group had significantly depressed PFC activity and circulating anti-SRBC Ab levels following the 13-week N2O exposures, and all 13-week exposure groups demonstrated decreased liver weights and leukopenia. Bone marrow activity at these dosing levels was depressed in a dose-dependent fashion following 13-week gas exposures.
Insights
Occupational exposure to nitrous oxide (N2O) at 5000 ppm for 13 weeks suppressed immune responses in mice, including antibody production and bone marrow activity. However, short-term N2O exposure initially decreased, then increased, lymphocyte proliferation.
Area of Science:
- Toxicology
- Immunology
- Occupational Health
Background:
- Subanesthetic levels of nitrous oxide (N2O) are known to suppress cell proliferation.
- Understanding the impact of N2O on immune function is crucial for occupational safety.
Purpose of the Study:
- To investigate the effects of varying N2O exposure levels and durations on immune cell activity and immunocompetency in male CD-1 mice.
Main Methods:
- Mice were exposed to 0, 50, 500, or 5000 ppm N2O for 6 hr/day, 5 days/week, for 2 or 13 weeks.
- Assessed [3H]-TdR uptake in splenic lymphocytes (mitogen-induced and mixed lymphocyte culture), antibody-mediated immunity (PFC assay, anti-SRBC Ab titer), and bone marrow activity (dUrdST).
Main Results:
- Two-week exposure to 5000 ppm N2O significantly decreased [3H]-TdR uptake in splenic lymphocytes.
- Thirteen-week exposure to 5000 ppm N2O resulted in depressed plaque-forming cell activity, reduced antibody titers, leukopenia, and decreased liver weights.
- Bone marrow activity was dose-dependently depressed after 13-week N2O exposure.
Conclusions:
- Prolonged occupational exposure to high levels of N2O can impair immune function and reduce organ weights.
- N2O exposure at 5000 ppm for 13 weeks negatively impacts both cellular and humoral immunity in mice.
- Further research is needed to establish safe occupational exposure limits for N2O.