Possible functional immunotoxicity of acrylonitrile (VCN).
Acrylonitrile (vinyl cyanide, VCN), an environmental pollutant, has been shown to be an animal and human carcinogen particularly for the GIT. In a previous work done in our laboratory, VCN induced immunosuppressive effects as indicated by a decrease in plaque forming cell (PFC) response to SRBCs (sheep red blood cell) immunization, a marked depletion 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 day-1) was given to CD-1 mice once daily for 5, 10 and 15 days. Immunohistochemical assessment of the number of cells capable of producing IgA in different intestinal compartments (duodenum, jejunum and ileum) revealed a significant decrease following VCN treatment. On the contrary, Bromodeoxyuridine (BrdU) incorporation in gut epithelial cells (duodenum and ileum) showed a significant increase in the same VCN-treated groups of animals. On the other hand, [3H]thymidine uptake was significantly 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 investigated parameters. The results suggested that VCN has a profound immunosuppressive effect either systemically or locally which could be a contributing factor in its GIT carcinogenicity.
Hamada
F M
FM
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Abdel-Aziz
A H
AH
Abd-Allah
A R
AR
Ahmed
A E
AE
D000181:Acrylonitrile / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D007070:Immunoglobulin A / Q000096:biosynthesis; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007421:Intestine, Small / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D002273:Carcinogens; D007070:Immunoglobulin A; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D008934:Mitogens; D010835:Phytohemagglutinins; D014316:Tritium; D003208:Concanavalin A; D000181:Acrylonitrile; D013936:Thymidine