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The Division of Hematology-Oncology, The Jewish Hospital of St. Louis, and Washington University School of Medicine, St. Louis, Missouri 63110
Imidoesters amidinate free amino groups and produce inter- and intramolecular covalent bonds. To determine whether imidoesters influenced lymphocyte transformation, human peripheral blood or calf lymph node lymphocytes were cultured with dimethyladipimate (DMA), a bifunctional (cross-linking) imidoester, or methyl acetimidate (MAC), a monofunctional (noncross-linking) imidoester. Both DMA and MAC decreased the rate of endogenous DNA synthesis in a dose-dependent fashion. In further work, lymphocytes were treated with Phaseolus vulgaris phytohemagglutinin, concanavalin A, or periodate. DMA (1 mM) decreased DNA synthesis in P. vulgaris phytohemagglutinin-stimulated human cells by 65%, Concanavalin A-stimulated cells by 98.2%, and periodate-stimulated cells by 85%. Similar results were obtained with 1 mM MAC. Inhibition by DMA was slightly greater than was the inhibition by MAC. Decreased DNA synthesis resulted if DMA was added to P. vulgaris phytohemagglutinin-stimulated human lymphocytes at initiation of culture (72%) or after 16 hr (75%); inhibition was less when DMA was added after 24 hr (43%) and was not apparent if added after 48 hr. Therefore, both monofunctional and bifunctional imidoesters inhibit endogenous and stimulated DNA synthesis in human and calf lymphocytes.
1 Supported in part by American Cancer Society Grant BC155, by USPHS Grant CA15621, by the Milton Moss Memorial Cancer Research Fund, by the Cancer Progress Fund of The Jewish Hospital, by the Multimodality Oncology Project of The Jewish Hospital, and by the Dr. Howard Alt Memorial Research Grant from the Leukemia Research Foundation.
2 To whom requests for reprints should be addressed, at Division of Hematology-Oncology. The Jewish Hospital of St. Louis, 216 South Kingshighway, St. Louis, Mo. 63110.
Received 6/12/78. Accepted 10/25/78.
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