Chloramphenicol induces abnormal differentiation and inhibits apoptosis in activated T cells.
Chloramphenicol is a broad-spectrum antibiotic used for the treatment of many infectious diseases and has become one of the major seafood contaminants. Hematologic disorders such as aplastic anemia and leukemia induced by chloramphenicol are a major concern. However, the mechanism underlying chloramphenicol-induced leukemogenesis is not known. By investigating the effects of chloramphenicol on the activation of mouse T cells stimulated with anti-CD3 antibody or staphylococcal enterotoxin B, we found that chloramphenicol induces the differentiation of activated T cells into lymphoblastic leukemia-like cells, characterized by large cell size, multiploid nuclei, and expression of CD7, a maker for immature T cells and T-cell lymphocytic leukemia, thus phenotypically indicating differentiation toward leukemogenesis. High expression of cyclin B1, but not p53, c-myc, and CDC25A, was detected in chloramphenicol-treated activated T cells, which may relate to abnormal cell differentiation. Chloramphenicol inhibited the activation-induced cell death of mouse and human T-cell receptor-activated T cells by down-regulating the expression of Fas ligand. Our findings show that abnormal cell differentiation and inhibition of apoptosis may contribute to the development of leukemia associated with clinical applications of chloramphenicol.
Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA.
Zeng-Rong
ZR
Yuan
Yufang
Y
Shi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D017252:CD3 Complex / Q000378:metabolism; D002454:Cell Differentiation; D002701:Chloramphenicol / Q000494:pharmacology*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced* / Q000473:pathology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C534699:CCNB1 protein, human; D017252:CD3 Complex; C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D011500:Protein Synthesis Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D002701:Chloramphenicol