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Immunosuppression by chronic exposure to N-nitrosodimethylamine (NDMA) in mice
R Desjardins1, M Fournier, F Denizeau
1Département des Sciences Biologiques, Université du Québec à Montréal, Canada.
Abstract:
Immunosuppression of humoral and cellular responses following chronic oral exposure to 1, 5, 10, and 20 ppm N-nitrosodimethylamine (NDMA) was examined in CD-1 mice. Monitoring of cumulative mortality and the incidence of peritoneal ascites in animals showed an NDMA dose-related mortality and hepatotoxicity. No visible changes in immunological parameters were noted at the 1 ppm NDMA dose. Immunosuppression of immunoglobulin M (IgM) antibody response by NDMA to sheep red blood cells (SRBC) was time-related, dose-related, and could be reversed within 30 d by removal of the chemical from the drinking water. Cellular immune response, monitored by allogeneic stimulation of cells in mixed lymphocyte reaction (MLR), was markedly suppressed by 10 and 20 ppm NDMA. Thus, chronic exposure to NDMA, except for the low-hepatotoxic doses of nitrosamine, resulted in a marked and persistent immunosuppression of cellular and humoral responses in CD-1 mice. In conclusion, chronic exposure to the hepatotoxic (ascite-inducing) doses of NDMA suppressed humoral and cellular immunity. The persistent immunosuppression could be reversed after the removal of NDMA from the drinking water. Although no direct NDMA-related cancer was reported in humans, our data point to a potential epigenetic carcinogenicity of nitrosamines due to chronic immunosuppression.
Insights
Chronic exposure to N-nitrosodimethylamine (NDMA) suppressed immune responses in mice. This immunosuppression, affecting both humoral and cellular immunity, was dose-dependent and reversible upon NDMA removal.
Area of Science:
- Toxicology
- Immunology
- Carcinogenesis
Background:
- N-nitrosodimethylamine (NDMA) is a chemical compound with known toxic effects.
- The impact of chronic NDMA exposure on the immune system is not fully understood.
- Investigating potential links between immunosuppression and carcinogenicity is crucial.
Purpose of the Study:
- To evaluate the immunosuppressive effects of chronic oral NDMA exposure in CD-1 mice.
- To determine the dose-response relationship and reversibility of NDMA-induced immunosuppression.
- To explore the potential for epigenetic carcinogenicity linked to NDMA-induced immune dysfunction.
Main Methods:
- Mice were orally exposed to varying doses of NDMA (1, 5, 10, 20 ppm).
- Humoral immunity was assessed by measuring immunoglobulin M (IgM) antibody response to sheep red blood cells (SRBC).
- Cellular immunity was evaluated using the mixed lymphocyte reaction (MLR) assay.
Main Results:
- NDMA exposure caused dose-related mortality and hepatotoxicity, indicated by peritoneal ascites.
- Immunosuppression of IgM antibody response to SRBC was observed, being time- and dose-dependent.
- Cellular immune response (MLR) was significantly suppressed at 10 and 20 ppm NDMA.
- Immunosuppression was reversible within 30 days after discontinuing NDMA exposure.
Conclusions:
- Chronic exposure to hepatotoxic doses of NDMA leads to marked and persistent immunosuppression of humoral and cellular immunity in mice.
- The observed immunosuppression is reversible upon removal of NDMA from the diet.
- Data suggest a potential for epigenetic carcinogenicity of nitrosamines due to chronic immunosuppression, even without direct evidence of NDMA-induced cancer.