POSSIBLE FUNCTIONAL IMMUNOTOXICITY OF ACRYLONITRILE (VCN)

Acrylonitrile (vinyl cyanide, VCN), an environmental pollutant, has be en shown to be an animal and human carcinogen particularly for the GIT . In a previous work done in our laboratory, VCN induced immunosuppres sive effects as indicated by a decrease in plaque forming cell (PFC) r esponse to SRBCs (sheep red blood cell) immunization, a marked depleti on of spleen lymphocyte subsets by flow cytometric analysis as well as bacterial translocation of the normal flora leading to brachial lymph node abscess. This work was carried out to evaluate the systemic and/ or local immunotoxic potential of VCN. Acrylonitrile (2.7 mg kg(-1) da y(-1)) was given to CD-1 mice once daily for 5, 10 and 15 days. Immuno histochemical assessment of the number of cells capable of producing I gA in different intestinal compartments (duodenum, jejunum and ileum) revealed a significant decrease following VCN treatment. On the contra ry, Bromodeoxyuridine (BrdU) incorporation in gut epithelial cells (du odenum and ileum) showed a significant increase in the same VCN-treate d groups of animals. On the other hand, [H-3]thymidine uptake was sign ificantly decreased in splenocytes stimulated with phytohemaglutinin ( PHA), Concanavalin-A (Con-A) and Lipopolysaccharide (LPS) and derived from animals treated with VCN. The effects of VCN were started after 5 days and increased up to 15 days of daily treatment in most of the in vestigated parameters. The results suggested that VCN has a profound i mmunosuppressive effect either systemically or locally which could be a contributing factor in its GIT carcinogenicity. (C) 1998 The Italian Pharmacological Society.