Growth mouse leukemia cells

Manzamine A is an alkaloid that was shown to inhibit the growth of P-388 mouse leukemia cells. The synthesis of the tetracyclic substructure of this natural product was reported by D.J. Hart. For the construction of the perhydroisoquinoline moiety, he utilized the Keck radical allylation. This transformation was carried out under standard conditions, reacting a secondary alkyl iodide with allyltributyltin. 

LIF (leukemia inhibitory factor) is a cytokine which inhibits the growth of mouse leukemia cells (Ml cells) and induces their differentiation into macrophages (Gearing et ah, 1987 Hilton et ah,... 

At nanomolar to micromolar concentrations, yessotoxin has been shown to be toxic to many mammalian cells in culture, including a BE(2)-M17 neuroblastoma cell line [37], a human neuroblastoma cell line [38], HeLa S3 cells [39], rat L6 and mouse BC3H1 skeletal muscle myoblast cell lines [40], P388 mouse leukemia cells [41], 3T3 mouse fibroblasts [42], rat hepatocytes [43], and isolated cerebellar neurons [44]. Yessotoxin did not cause significant mortality in MCE breast cancer cells at nanomolar concentrations, although growth was inhibited [45]. Toxicity to an insect cell line (IPLB-LdFB), derived from a lepidopteran larval fat body, has also been demonstrated [42]. 

Overexpression of PKC( has been reported to be required for mitogenic maturation of Xenopus oocytes and led to deregulation of growth control in mouse fibroblasts (Berra et al., 1993). However, these effects of PKC in Xenopus oocytes seem not to be clear (Carnero et al., 1995). In U937 monocytic leukemia cells PKC( overexpression decreased proliferation rate and saturation density, indicating the induction of differentiation (Ways et al.,... 

Pretazettine (395) has been the subject of numerous biological studies, and it has been shown to exhibit a number of interesting activities (96,97,101,178-187). For example, 395 was found to inhibit HeLa cell growth as well as protein synthesis in eukaryotic cells by interfering with the peptide bond formation step (97,101). Furthermore, pretazettine inhibited the purified RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus, a typical C-type virus (178), in an unusual fashion since it physically combined with the polymerase enzyme itself rather than interacted with the nucleic acid template. Pretazettine also exhibited antiviral activity against the Rauscher leukemia virus in mouse embryo cell cultures by suppressing viral replication (179). 

The title substituted 6 phenylpurine bases and nucleosides 10—13, as well as some acetyl derivatives 8, were tested on their in vitro inhibition of the cell growth in the following cell cultures mouse leukemia L1210 cells (ATCC CCL 219) murine L929 cells (ATCC CCL 1) human cervix carcinoma HeLa S3 cells (ATCC CCL 2.2) and human T lymphoblastoid CCRF-CEM cell line (ATCC CCL 119). Only substituted 6-phenylpurine ribonucleosides 12 and their triacetates 8 exhibited significant activity in these assays (Table 1), while the bases 10 and 11, as well as the 2 amino 6 phenylpurine ribonucleosides 13, were entirely inactive. 

To find whether the reduced foci formation was due to inhibition of MSV (M) replication, the effect of these compounds on virus growth was studied. Secondary mouse embryo cell cultures were infected with MSV (M) at the rate of 0.03 competent MSV infectious units per cell and treated with the compounds at different doses after the infection by the focus assay in the presence of an optimal amount of MLV (M) (1.01 10s Leukemia Vims Helper Units) according to Hirschman etal.33 Similarly treated uninfected cultures were trypsinized at the same time, and cells were counted. 

While the general DNA polymerase activity found in T. spiralis muscle larvae crude extract was 0.7 0% mnol/h/mg protein (N = 2), the corresponding activity assayed under conditions preferred by DNA polymerase a was 4.6 74% nmol/h/mg protein (N = 2). As a reference, the two sets of assay conditions were used with crude extracts from mouse leukemia L1210 cells (harvested in the logarithmic phase of growth) and the corresponding activities determined as 1.4 nmol/h/mg protein (N = 1) and 3.7 mnol/h/mg protein (N = 1), respectively. 

Our application is to mouse L-1210 leukemia cells where it is observed experimentally that essentially exponential growth occurs during the main middle portion of cell growth (see Reference 16). An asymptotic solution for this case can be developed by assuming a functional form ... 

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