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Correlation between Human Cell Growth Response to Interleukin 1 and Receptor Binding¹

Department of Molecular and Cell Biology, The Pennsylvania State University, University Park, Pennsylvania 16802 [E. V. G., S-C. T., T. L., S. E. L.], and Cistron Biotechnology, Pine Brook, New Jersey 07058 [G. K.]

Human recombinant interleukin 1 (IL-1) and IL-1ß inhibited the replication of the mammary tumor cell line, MDA-MB-415; stimulated division in the colon carcinoma, SW-48; and had no effect on the growth of the milk mammary line, HBL-100. Inhibition of growth was reflected in a significant decrease in DNA synthesis accompanying a transient increase in RNA synthesis. Specific binding of ¹²⁵I-labeled recombinant IL-1ß by MDA-MB-415 and SW-48 reached a maximum by 2 h of incubation, and an equivalent amount was bound by each cell type. Binding was inhibited in a dose-dependent manner by unlabeled IL-1 or IL-1ß. Scatchard plot analysis revealed that MDA-MB-415 cells expressed approximately 700 binding sites with an apparent dissociation constant of 8.8 x 10^-10 M. Reversibility of growth inhibition was independent of dose or time of incubation, but DNA synthesis did not return to control values. Flow cytometric analysis of DNA content showed that growth inhibition was cell cycle phase nonspecific with a slight reduction in the proportion of cells in S phase. The major conclusion from these studies was that inhibition or stimulation of malignant cell growth by IL-1 was related to the presence of receptor sites.

¹ Supported in part by Grants CA 44677 and CA 45143 from the Department of Health and Human Services.

² To whom requests for reprints should be addressed, at 306 South Frear Building, University Park, PA 16802.

Received 12/29/87. Revised 4/27/88. Revised 6/29/88. Accepted 7/ 6/88.

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