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Decreased Immunoglobulin Production by a Human Lymphoid Cell Line following Melphalan Treatment¹

Health and Safety Research [G. D. G., B. A. O.] and Biology [G. D. N.] Divisions, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830; Department of Physics, University of Illinois, Chicago, Illinois 60680 [C. E. A.]; and Department of Medicine, College of Medicine/Knoxville Unit, University of Tennessee Center for the Health Sciences, Knoxville, Tennessee 37920 [A. S.]

The effect of melphalan on immunoglobulin G (IgG) production by a human lymphoblastoid cell line (BF) was studied. The amount of secreted IgG and the percentage of cells containing cytoplasmic IgG were measured by immunoassay and cytofluorometry, respectively. Dose-response studies indicated that melphalan concentrations of 2 x 10^-8 M had no effect, while concentrations of 8 x 10^-7 M were totally toxic, after 72-hr exposures to the drug. Statistically significant, persistent, alterations in both synthesis and secretion of IgG by BF cells were observed following treatment for 72 hr with 4 x 10^-7 M melphalan, and there was an increase in population-doubling time from 24 to 72 hr in these drug-treated cells. The percentage of IgG-containing cells in melphalan-treated cultures was significantly decreased as compared to control cultures. IgG secretion was also decreased in these cultures, and the variation in IgG secretion as a function of cellular growth was significantly altered following melphalan treatment. Decreased IgG production following melphalan treatment may be related to altered cell cycle kinetics. Based on immunological analysis, there was no evident alteration in the IgG secreted by melphalan-treated cells, nor did melphalan treatment produce a cellular population lacking IgG entirely.

¹ Research sponsored by the Exploratory Studies Program at Oak Ridge National Laboratory and the Office of Health and Environmental Research, United States Department of Energy under Contract W-7405-eng-26 with the Union Carbide Corporation.

² To whom requests for reprints should be addressed, at P. O. Box X, Building 4500S, Room F-250, Oak Ridge, Tenn. 37830.

³ Supported by a stipend under the Summer Research Internship Program at Oak Ridge National Laboratory during his work on the project.

⁴ Recipient of USPHS Research Grant CA10056.

Received 4/19/82. Accepted 7/30/82.