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Induction of Tubuloreticular Inclusions in Human Lymphoma Cells (Raji Line) Related to S-Phase Treatment with Halogenated Pyrimidines¹

Clinical Pathology Laboratories, Division of Laboratories and Research, New York State Department of Health, Albany, New York 12201 [B. H., P. M. G.], and the Bureau of Biologics, Food and Drug Administration, Bethesda, Maryland 20014 [D. W. B.]

Formation of tubuloreticular inclusions (TRI) within the endoplasmic reticulum was initiated in human lymphoma cells (Raji line) by exposure of synchronized cultures to 5-bromo-2'-deoxyuridine (BUdR) for all or portions of a single S phase. The TRI were detected by electron microscopy as early as 36 hr after addition of 260 µM BUdR. By 72 hr, thin-section counts of TRI reached a maximum at circa 30% of cell cross-sections, which was estimated to represent no less than one TRI per two whole cells. Although the numbers of TRI depended upon the concentration of halogenated pyrimidine, cell division was not prerequisite to their appearance, and exposure of the cells to BUdR for repeated cycles of DNA synthesis did not increase the maximal level. These results were consistent with a unifilar dominance and modified regulation of gene expression, rather than transcription of an altered DNA. Raji cells exposed to equimolar thymidine as controls to each experiment, as well as untreated Raji cells, were uniformly negative for TRI. A relation of TRI induction to metabolism of BUdR was indicated by competitive inhibition with thymidine and lack of response in a subline selected for BUdR resistance. There was no evidence for previously postulated relationships of TRI to myxovirus infection or IgG production. In vitro induction of TRI can serve as an experimental model for further investigations into the significance of TRI found in lymphocytes of patients with systemic immune diseases or neoplasms.

¹ The work was supported in part by the Food and Drug Administration Contract FDA-74-27. Portions of this work were presented at the 14th Annual Meeting of the American Society for Cell Biology, November 21 to 23, 1974, San Diego, Calif. (Hulanicka, B., Grimley, P. M., Almy, R. E., Perecko, J. P., and Kawka, D. Induction of Tubular Structures in the Endoplasmic Reticulum of Synchronized Human Lymphoid Cells following One S-Period in 5-BUdR (Abstract 298). Abstracts Fourteenth Annual Meeting American Society for Cell Biology. J. Cell Biol. 63: 149a, 1974.)

² Present address: Polish Academy of Sciences, Wroclaw, Poland.

³ Presenter. To whom requests for reprints should be addressed.

Received 9/27/76. Accepted 4/14/77.