Immunosuppression by chronic exposure toN‐nitrosodimethylamine (NDMA) in mice

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.

Evaluation of Hematological and Immunological Parameters in Mice Exposed to Sublethal and Subchronic Doses of Dimethoate

“…Our ndings agree with those of Stahlman (1992) who found a dose-dependent decrease in IgG in rats after acyclovir exposure and with Banerjee et al (1996) who found that aldrin and DDT suppress both IgG and IgM levels to the pesticide-exposed rats. However, our ndings contrast with Fournier et al (1992) and Desjardins et al (1992) who reported suppression of primary humoral response N-nitrosodimethylamine and atrazine treatment.…”

Hazardous air pollutants and asthma.

“…Carcinogenic compounds can cause irritation and inflammation at sites of exposure and are often antigenic (251)(252)(253)(254)(255)(256)(257)(258)(259). Respiratory carcinogens (or suspected carcinogens) include antimony compounds (260)(261)(262)(263), arsenic compounds (263)(264)(265)(266)(267)(268), hexamethylphosphoramide (269,270), 4,4´-methylene-bis(2-chloroaniline) (271,272), bromoform (273,274), methylene chloride (275), 4,4´-methylenedianiline (276,277), nitrobenzene (mice) (278-280), 4-nitrobiphenyl (281), 2-nitropropane (282)(283)(284)(285), N-nitroso-Nmethylurea (286), N-nitrosodimethylamine (287)(288)(289)(290), N-nitrosomorpholine (291-293), pentachlorophenol (mice) (294,295), polycyclic aromatic hydrocarbons (250,254,255), 1,3-propane sultone (296,297), propylene oxide (298-300), 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) (301-305), 2,4-toluene diamine (306,307), viny...…”

Comparison of humoral and cell mediated immune response modulation by chemical and bio‐pesticides

“…[7] and Desjardins et a/. [8] who reported suppression in only the primary humoral response with N-nitrosodimethylamine and atrazine treatment. In the present study, Neemazal did not suppress the primary or secondary antibody response.…”