Effects of N-nitrosodimethylamine on cell-mediated immunity

Dimethylnitrosamine (DMN) exposure altered the cell-mediated immune response of B6C3F1 adult female mice as assessed by several immunological assays. Following 14 daily exposures (i.p.) to 1.5, 3.0, or 5.0 mg DMN/kg, mice exhibited a depression in their lymphoproliferative response to the T-cell mitogens concanavalin A and phytohemagglutinin, and in their mixed lymphocyte response to mitomycin-treated DBA-2 spleen cells. The delayed hypersensitivity response (DHR) to keyhole limpet hemocyanin (KLH), as measured by vascular permeability changes, was decreased by over 50% at the 5.0-mg/kg dose. When the DHR to KLH was measured by an influx of endogenously 125I-iododeoxyuridine (IUdR)-labelled monocytes, there was a 300% increase in the response of the 5.0-mg-DMN/kg group. Adoptive transfer studies using exogenously radiolabelled (51Cr) bone marrow cells from either vehicle- or DMN-treated (5 mg/kg) donors indicated a greater than 60% reduction in the DHR to KLH in DMN-treated mice (5.0 mg/kg level) regardless of the donor treatment. Animals exposed to DMN exhibited a decreased susceptibility to Listeria monocytogenes. The dichotomy in the results of the KLH DHR measured by monocyte influx and the increased resistance to the bacterial challenge were interpreted to reflect an effect on bone marrow. The numbers of granulocyte/monocyte stem cells were increased in a dose-related fashion in bone marrow from DMN-treated mice. The results indicate that DMN-treatment impairs cell-mediated immunity while increasing the number of bone marrow cells differentiating to form granulocytes or monocytes with an apparent enhancement in functional activity.