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 chloram...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2008-06, Vol.68 (12), p.4875-4881
Main Authors: Yuan, Zeng-Rong, Shi, Yufang
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Blotting, Northern
CD3 Complex - metabolism
Cell Differentiation
Chloramphenicol - pharmacology
Cyclin B - metabolism
Cyclin B1
Flow Cytometry
Humans
Mice
Mice, Inbred BALB C
Precursor Cell Lymphoblastic Leukemia-Lymphoma - chemically induced
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Protein Synthesis Inhibitors - pharmacology
Proto-Oncogene Proteins c-myc - metabolism
Spleen - cytology
Spleen - drug effects
Spleen - metabolism
T-Lymphocytes - drug effects
T-Lymphocytes, Regulatory - pathology
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-07-6061