Novikoff hepatoma

Olson MO, Ezrailson EG, Guetzow K, Busch H (1975) Localization and phosphorylation of nuclear, nucleolar and extranucleolar non-histone proteins of Novikoff hepatoma ascites cells. J Mol Biol 97 611-619... 

Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg D (1998) FACT, a factor that facilitates transcript elongation through nucleosomes. Cell 92 105-116 Orrick LR, Olson MO, Busch H (1973) Comparison of nucleolar proteins of normal rat Uver and Novikoff hepatoma ascites cells by two-dimensional polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 70 1316-1320... 

Wilkinson DS, Pitot HC. Inhibition of ribosomal ribonucleic acid maturation in Novikoff hepatoma cells by 5-fluorouracil and 5-fluorouridine. J Biol Chem 1973 248 63-68. 

Fig. 12.3. Time course of sonographic enhancement by LCM of Novikoff hepatoma in anesthetized rats using an immobilized transducer. These representative rat liver scans were obtained before injection, and 2, 30, and 60 minutes after i.v. injection, respectively. Arrows indicate the relatively bright, contrast-enhanced tumor area in the liver (within the image plane) at 2 minutes after injection. Contrariwise, the same area before injection (first panel) is only slightly hyperechoic compared with the surrounding normal liver parenchyma. (Taken from ref. 528.)...

Fig. 12.4. Demonstration of tumor targeting ability of LCM after i.v. injection into a rat bearing Novikoff hepatoma. All histologic sections were stained with Oil Red-O and counterstained with hematoxylin. (Top panel) A low-power view of the hepatoma and surrounding normal liver tissue. (Bottom panels) High-power insets of the neighboring normal liver parenchyma (bottom left) and the Novikoff hepatoma itself (bottom right). The lipid-coated microbubbles can be appreciated as solid black discs ranging in size from submicron up to 4 or 5 pm. (Taken from ref. 528.)...

There is an increased blood flow in brain tumors (ref. 589), and the blood-brain barrier is leaky in and around 9L tumors because the blood vessels associated with these (ref. 568), and other (ref. 565-567), tumors are fenestrated. This well-known leakiness of tumor capillaries, which in the case of brain tumors includes breaches in the blood-brain barrier (ref. 566,568 cf. Section 12.2), would allow extravasation of small particulate matter (cf. ref. 590-594) or LCM. Once in the tumor area, LCM remain there because of an affinity for tumor cell surface components (cf. ref. 531 see also Chapter 14). At least 4 different types of experimental tumors in rats (C6 glioma, 9L gliosarcoma, Novikoff hepatoma, and Walker-256 carcinosarcoma), as well as several spontaneous tumors in dogs (ref. 570), do interact with LCM in a preferential manner (cf. Chapters 12 and 13), suggesting that LCM affinity may be for tumor cells in general (ref. 531). 

Unlike 6-mercaptopurine and 6-thioguanine, 8-azaguanine difiused into Novikoff hepatoma cells (rat) without any sign of saturability, indicating that no carrier was involved. By varying the pH, it was shown that only the nonionized form entered the cell. 9-a-D-Arabinofuranosyl-8-azaadenine was found toxic to human epidermoid carcinoma cells in culture, whereas... 

The nonintercalative drugs VP-16 and VM-26 and related compounds have also been shown to induce DNA breaks by the type II topoisomerase from Novikoff hepatoma cells (Minocha and Long,... 

Several topoisomerases have been shown to be substrates for protein kinases. Nuclear extracts from a human cell line contain a protein kinase which phosphorylates DNA topoisomerase I from the same cell line (Mills et al., 1982). The type I topoisomerase purified from Novikoff hepatoma cells was found to be a phosphoprotein (Durban et al., 1983). Treatment with alkaline phosphatase dephosphorylates the enzyme and reduces its DNA-relaxing activity. Subsequent treatment with protein kinase restores the activity of the topoisomerase to its original level (Durban et al., 1983). 

Greenberg, N., Schumm, D.E., and Wehh, T.E. (1977) Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine-sensitive and -resistant cell lines of the Novikoff hepatoma. The Biochemical Journal, 164 (2), 379-387. 

Thioredoxin systems have also been demonstrated in L. leichmannii (39), rat Novikoff hepatoma (40), T4 phage infected E. coli (41, 42), yeast (43), rat liver (44), calf liver (45) and germinating wheat embryo (32). 

The thioredoxin reductases are highly specific for their thioredoxin substrate. For instance, yeast thioredoxin reductase is specific for the reduction of the homologous thioredoxins and does not interact with thioredoxins from E. coli or from T4-infected E. coli. Furthermore E. coli thioredoxin reductase does not use the thioredoxins from Novikoff hepatoma, yeast, and L. leichmannii. 

Pyrazomycin. Pyrazomycin (11), 3-(l-p-D-ribofuranosyl)-4-hydroxypyrazole 5-carboxamide, is isolated from S. Candidas (1—4,9,10). The incorporation of [2-13C]acetate and [1- and U-14C]glutamate into the four contiguous carbons of pyrazomycin has been reported (11,12). Pyrazomycin 5 -phosphate inhibits orotidylic acid decarboxylase. Pyrazomycin inhibits adenosine phosphorylation and decreases the incorporation of deoxyuridine into DNA of Novikoff hepatoma cells in culture. It also inhibits the growth of tumor cells and the cytopathic effects of vaccinia, herpes simplex, vesicular stomatitis, Newcasde disease, measles, Sindbis, polio, hepatitis A, and coxsackie viruses (13,14). The inhibitory action of (11) on viral multiplication is reversed by uridine. 

L-[amide-Asparagine has been prepared in radiochemical yields of 10-20%, in a reaction catalyzed by asparagine synthetase purified from extracts of rat Novikoff hepatoma (29) or from Escherichia coU (30). Neither enzyme preparation is presently available from commercial sources. 

The topology of the radical site pocket of calf thymus and mouse fibroblast ribonucleotide reductase was recently probed with a series of hydroxamate inhibitors of increasing bulkiness and will be discussed in the following section. Other mammalian sources from which ribonucleotide reductases have been isolated and more or less purified include rat Novikoff hepatoma and regenerating rat liver" rabbit bone mar-row 5,66) Ejjj-iich ascites tumor cells of mice and cultured human lymphoblast cells Some of their properties are described in Table 2. Many more animal and human cells were assayed for enzyme activity, frequently in mutant cell lines, to test for cell cycle dependence, mechanisms of metabolic regulation, drug resistance, and correlation with tumor growth rates. Representative studies of this kind, which rapidly expand in number, are summarized in Table 3. 

Novikoff hepatoma of rat 6 X 10- reversible without metal addition 282, 283... 

Novikoff hepatoma of rat embryonal chicken brain human tumor cells Scenedesmus obliquus inactive with S. cerevisiae and probably E. coli enzyme... 

Novikoff hepatoma of the rat and for antineoplastic activity in mice bearing either 6-thiopurine-sensitive or -resistant cells of Sarcoma 180. Structure-activity relationship studies have delineated the bulk requirement for a five-membered ring at 4 -position for optimum alkaline phosphatase-inhibitor interaction. The presence of this bulk resulted in loss of inhibitory activity by a-(A0-hetero-cyclic carboxaldehyde thiosemicarbazones for ribonucleoside diphosphate reductase. However, some of these agents were found to have retained tumour-inhibitory activity. 4 -Substituted thiosemicarbazides, the intermediates employed for the syntheses of corresponding thiosemicarbazones, were prepared by the procedures of McElhinney [24], except that reaction of ethyleneimine was not successful with methyl dithiocarbazate therefore, the ethyleneimine derivative (39) was obtained first by forming the corresponding methyl dithiocarbazate ester (38) and then by reacting it with ethyleneimine. 

In a general sense, reduced thioredoxins appear to be capable of serving as reductants to heterologous ribonucleotide reductases. For example, the E. coli thioredoxin will function as a hydrogen donor for the ribonucleotide reductase of the Novikoff hepatoma, and yeast thioredoxin will serve the E. coli reductase. On the other hand, reduction of any particular thioredoxin is catalyzed only by the homologous thioredoxin reductase, that is, both must be obtained from the same organism. 

The reduction of ribonucleotides by enzymes from animal cells was first demonstrated by Beichard and co-workers with crude preparations from chick embryo the four common ribonucleotides were reduced and evidence for modulation of activity by nucleotides was obtained (30). The Novikoff hepatoma of the rat has been the source of a partly purified preparation of ribonucleotide reductase that has enabled deoxyribonu-cleotide sjmthesis to be studied in considerable detail the work of Moore and colleagues has shown that this process has many similarities to that in E. coli 31, 32). 

Smetana, K., Unuma, T., Busch, H. Ultrastructural studies on nucleic acids of nucleolar granular components in Novikoff hepatoma cells. Exp. Cell Res. 51, 105-122 (1968)... 

The formation of cytidylic acid from uridylic acid was studied in a Novikoff hepatoma and E. colL In E. coli, glutamine appears to be the primary amino donor for cytidylic acid synthesis, and the synthesis occurs after uridylic acid has been converted to the triphosphate in the presence of ATP. The detailed mechanism of the amination of UTP to yield CTP... 

In an attempt to examine some properties of cancer cells we have measured the ability of Novikoff hepatoma to take up the saturated and "essential fatty acids" from the host and the capacity of this tumoral tissue to distribute these acids between the different lipid fractions. pH -glycerol was also used as a marker for "de novo" glycerolipid biosynthesis. 

The solid Novikoff hepatoma was maintained by intraperitoneal implants into male Holtzman rats and they were used 5 days after transplanting the tumor. Normal rat liver was obtained from rats of the same breed. 

Fig. 1. Ph I-glycerol and 11- Cj-stearic acid incorporation into total lipids from normal liver, host liver and Novikoff hepatoma.

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