Immunosuppression by chronic exposure toN‐nitrosodimethylamine (NDMA) in mice
作者:
Richard Desjardins,
Michel Fournier,
Francine Denizeau,
Krzysztof Krzystyniak,
期刊:
Journal of Toxicology and Environmental Health
(Taylor Available online 1992)
卷期:
Volume 37,
issue 3
页码: 351-361
ISSN:0098-4108
年代: 1992
DOI:10.1080/15287399209531676
出版商: Taylor & Francis Group
数据来源: Taylor
摘要:
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 persistant 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.
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