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Biochemical and autoradiographic evidence show both glycogen synthesis and the presence of glycogen synthase (UDP glucose [UDPG] : glycogen 4-a-D-glucosyltransf erase; EC 2.4 .1 .11) in isolated nuclei of Ehrlich-Lettre mouse ascites tumor cells of the mutant subline H D33. 5 d after tumor transplantation, glycogen (average 5-7 pg/cell) is stored mainly in the cell nuclei . The activity of glycogen synthase in isolated nuclei is 14 .5 mU/mg protein. At least half of the total cellular glycogen synthase activity is present in the nuclei . The nuclear glycogen synthase activity exists almost exclusively in its b form . The K,, value for (a + b) glycogen synthase is 1 x 10-3 M UDPG, the activation constant is 5 x 10 -3 M glucose-6-phosphate (Glc-6-P) .Light and electron microscopic autoradiographs of isolated nuclei incubated with UDP-[1-3 H]glucose show the highest activity of glycogen synthesis not only in the periphery of glycogen deposits but also in interchromatin regions unrelated to detectable glycogen particles. Together with earlier findings on nuclear glycogen synthesis in intact HD33 ascites tumor cells (Zimmermann, H .-P., V. Granzow, and C. Granzow. 1976 . J. Ultrastruct. Res. 54 :115-123), the results of tests on isolated nuclei suggest a predominantly appositional mode of nuclear glycogen deposition, without participation of the nuclear membrane system .In intact cells, synthesis of UDPG for nuclear glycogen synthesis depends on the activity of the exclusively cytoplasmic UDPG pyrophosphorylase (UTP : a-D-glucose-1-phosphate uridylyltransferase ; EC 2.7 .7 .9) . However, we conclude that glycogen synthesis is not exclusively a cytoplasmic function and that the mammalian cell nucleus is capable of synthesizing glycogen .Intranuclear glycogen deposition has been observed in amphibian (19), avian (11), and a variety of mammalia cells, particularly in hepatocytes (5,28,30,38), cells of renal collecting tubules (6), and cardiac muscle cells (8), partly under normal, partly under various pathological conditions . With respect to the origin of intranuclear glycogen, translocations of cytoplasmic glycogen particles into the nuclear compartment (30,40) free wild-type Ehrlich-Lettrt; ascites tumor, which was manipulated pharmacologically by means of N-methyl-colchicamide (27). A genome mutation of HD33 cells is associated with various phenotypical deviations from the wild type,' among which a pronounced nuclear and/or cytoplasmic glycogen storage is the most conspicuous (46). Characteristically, between days 4 and 6 after transplantation, glycogen deposits of increasing size are located chiefly within the tumor cell nuclei . Additional cytoplasmic glycogen storage is restricted to later stages oftumor development (46). On days 5 and 6, pronounced nuclear glycogen storage coincides with minimal cytoplasmic glycogen deposition in interphase cells . Thus, cells at this stage of tumor development provide a unique substrate for an analysis of their nuclear glycogen metabolism.In previous communications (...

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Despite many advances in predictive testing of human malignancies, we are far from using it routinely in clinical practice. Investigating the responsiveness of solid tumors to cytostatic drugs is particularly challenging. Nevertheless, for head and neck cancer, chemosensitivity testing is an increasingly attractive option, since chemotherapy has proven to have curative potential in the therapy of head and neck cancer, in particular in combination with radiation. The significant need for predictive methods to identify patients responsive to therapy, first of all in organ preservation programs, which is an alternative to first-line surgery, had recently renewed the discussion on a possible role of chemosensitivity testing in head and neck cancer. In this review, we discuss the current state of chemosensitivity testing in head and neck cancer. Recent methodological developments, in particular elimination of photochemical artifacts and inclusion of stromal cell response studies, may soon augment the value of ex vivo chemosensitivity testing for the management of head and neck cancer.