Effect of doxorubicin on mouse hybridoma B cells: stimulation of immunoglobulin synthesis and secretion.
The purpose of these studies was to investigate whether the cell-differentiating effect of anthracyclines can trigger an over-production and secretion of molecules that may interfere with the tumor-host relationship. We exposed mouse hybridoma B-cells, which are devoted to immunoglobulin production, to doxorubicin (10-40 ng/ml). We found that most doxorubicin-treated cells secreted 3- to 5-fold higher amounts of immunoglobulin than untreated cells, along with an accumulation of 50% of them in the G2+M phase of the cell cycle. The antigenic specificity of the immunoglobulin and its size pattern as determined by polyacrylamide gel electrophoresis were similar whether or not cells were treated with doxorubicin. The enhancement of immunoglobulin secretion by doxorubicin was associated with an increase of the intracellular pool of heavy and light chains of the immunoglobulin. Furthermore, an elevated synthesis of immunoglobulin was observed. The synthesis of other proteins also appeared to be modified in these circumstances. These data suggest that doxorubicin can potentiate the biological functions of target cells when used at low concentrations, elevating the production and secretion of effector molecules that interfere with the tumor-host relationship.
Teillaud
J L
JL
Laboratoire d'Immunologie Cellulaire et Clinique, INSERM U.255, Institut Curie, Paris, France.
Fourcade
A
A
Huppert
J
J
Fridman
W H
WH
Tapiero
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D006825:Hybridomas / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007700:Kinetics; D051379:Mice; D014176:Protein Biosynthesis
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D004317:Doxorubicin