Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of several chemical agents on the mutation frequency from asparagine dependence to asparagine independence has been studied in Jensen sarcoma cells. It was found that ethylmethanesulfonate brought about a dramatic exponential increase, while nitrosoguanidine was not lighly effective as a mutagen, causing only a modest increase in mutation frequency, and quinacrine HCl was ineffective. The results presented here are compared with those obtained in other systems and with our previous work on the effects of UV on mutation induction in the asparagine system. They suggest that the basis of the asparagine requirement of mammalian cell lines resides in a specific genetic alteration in nuclear DNA which is corrected by the mutagenic action of the agents tested here.
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PMID:Mutagenesis studies on cultured mammalian cells. The sensitivity of the asparagine-requiring phenotype to several chemical agents. 17 65

1. The oxidation of putrescine in vitro by pig kidney diamine oxidase (EC 1.4.3.6) was increased in the presence of 2-oxosuccinamic acid and malonamic acid. 2. It was inhibited by 3-aminopropionamide, oxaloacetate and pyruvate. 3. 2-Oxosuccinamate was derived from asparagine in virus-transformed baby hamster kidney (BHK) cells growing in tissue culture. 4. Asparagine was decarboxylated more efficiently by transformed than by normal BHK cells. 5. In BHK cells transformed by polyoma virus (Py BHK), 2-oxosuccinamate is the most likely immediate precursor of the 14CO2 arising from [U-14C]asparagine, and there was some evidence for its formation in an asparagine-dependent clone of BHK cells before and after their transformation by hamster sarcoma virus (respectively Asn- and HSV Asn-). 6. The relationship between 2-oxosuccinamate and pyruvate and the possible roles of these two substances in controlling cellular diamine oxidase activity are discussed.
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PMID:Modification of diamine oxidase activity in vitro by metabolites of asparagine and differences in asparagine decarboxylation in normal and virus-transformed baby hamster kidney cells. 18 27

Variations in ploidy do not affect the spontaneous mutation rate to asparagine non-requirement in Jensen rat sarcoma cells cultivated in vitro.
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PMID:Effect of ploidy on spontaneous mutation rate to asparagine non-requirement in cultured cells. 23 29

The N-[p-(fluorosulfonyl)benzyl] derivatives of L-asparagine and L-glutamine (1a,b) were synthesized as potential inhibitors of L-asparagine synthetase (ASase). Condensation of p-(fluorosulfonyl)benzylamine (2) with the suitably protected amino acid in the presence of dicyclohexylcarbodiimide, followed by deblocking, afforded 1a and 1b. Derivatives 1a and 1b at 10 mM inhibit ASase isolated from Novikoff hepatoma (rats) by 60 and 46%, respectively. Preliminary results on inhibition of Jensen sarcoma (L-asparaginase sensitive) and JA-1 sarcoma (L-asparaginase resistant) tissue cultures by 0.3 mM 1a (139,90%) and 1b (101, 103%), respectively, are discussed.
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PMID:Potential inhibitors of L-asparagine biosynthesis. 3. Aromatic sulfonyl fluoride analogs of L-asparagine and L-glutamine. 24 24

Hybrids were produced between the Indian muntjak fibroblasts and rat Jensen sarcoma cell line (JF1) auxotrophic for asparagine. They were selected without cloning under conditions providing survival of parental Indian muntjak and hybrid cells. This allowed to compare the Indian muntjak chromosome variability in the parental cells and hybrids under identical culture conditions. The frequency of muntjak chromosome aberrations proved to de higher in the hybrids (up to 47%) than in the parental cells (6.5%). Predominant are chromosomal breaks and dicentrics. The latter are mainly formed by fusion of chromosomes 1 and 2. The most fragile are 1 and X-chromosomes. Chromosomal breaks are evenly distributed along chromosome 1, and "hot" points are observed in X-chromosome. Possible mechanisms of the Indian muntjak chromosome rearrangements induced by somatic cell hybridization are discussed.
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PMID:[The chromosome variability of the Indian muntjac in somatic cell hybrids]. 182 94

Asparagine synthetase cDNAs containing the complete coding region were isolated from a human fibroblast cDNA library. DNA sequence analysis of the clones showed that the message contained one open reading frame encoding a protein of 64,400 Mr, 184 nucleotides of 5' untranslated region, and 120 nucleotides of 3' noncoding sequence. Plasmids containing the asparagine synthetase cDNAs were used in DNA-mediated transfer of genes into asparagine-requiring Jensen rat sarcoma cells. The cDNAs containing the entire protein-coding sequence expressed asparagine synthetase activity and were capable of conferring asparagine prototrophy on the Jensen rat sarcoma cells. However, cDNAs which lacked sequence for as few as 20 amino acids at the amino terminal could not rescue the cells from auxotrophy. The transferant cell lines contained multiple copies of the human asparagine synthetase cDNAs and produced human asparagine synthetase mRNA and asparagine synthetase protein. Several transferants with numerous copies of the cDNAs exhibited only basal levels of enzyme activity. Treatment of these transferant cell lines with 5-azacytidine greatly increased the expression of asparagine synthetase mRNA, protein, and activity.
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PMID:Isolation of human cDNAs for asparagine synthetase and expression in Jensen rat sarcoma cells. 288 7

Previous studies from this laboratory have demonstrated that growth of the methylcholanthrene (MCA) sarcoma is dependent on total nitrogen substrate availability in vivo and on the specific amino acids asparagine and glutamine in vitro. This experiment determines whether these two phenomena can be used to selectively depress tumor growth and maintain host carcass. Sixty-two rats were inoculated with sarcoma and were infused for 10 days with isocaloric (60 kcal/day) TPN solutions at 100%, 16%, 10%, and 5% of normal nitrogen levels, either with (W) or isonitrogenously without (WO) the amino acids asparagine, glutamine, aspartic acid, and glutamic acid. W solutions contained 33% of these amino acids. Mean weights of 100 W tumors were significantly greater (p = 0.002) than all other groups. Total body weights minus tumor weights were similar in W versus WO animals at each rate of nitrogen infusion. Mean venous plasma concentrations of asparagine, aspartic acid, glutamine, and glutamic acid were similar in all eight groups. These data indicate that the same degree of tumor depression produced by nitrogen deprivation can also be produced by removal of asparagine, glutamine, and their precursors from nutrient solutions without adverse effects on carcass mass. The mechanisms involved are not readily explained by analysis of venous plasma amino acid concentrations.
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PMID:Influence of total nitrogen, asparagine, and glutamine on MCA tumor growth in the Fischer 344 rat. 289 15

In comparisons of [3H]mannose-labelled glycopeptides from chick-embryo fibroblasts infected and transformed with non-defective Prague C Rous-sarcoma virus and from untransformed fibroblasts infected with a transformation-defective derivative of Prague C Rous-sarcoma virus, we have detected transformation-dependent alterations in both the acidic-type and the neutral-type asparagine-linked oligosaccharides of cellular glycoproteins. Pronase-digested glycopeptides were analysed by the combined techniques of gel filtration, exo- and endo-glycosidase digestion and concanavalin A-agarose affinity chromatography. The transformed cell glycoproteins contained more sialic acid and were enriched for more highly branched (versus biantennary) acidic-type structures compared with the untransformed cell glycoproteins, similarly to previously reported transformation-dependent alterations. In addition, the glycopeptides from the virus-transformed cells contained several neutral-type structures that were apparently absent from the untransformed cells: small neutral-type oligosaccharides (Man3GlcNAc2) that were sensitive to endo-beta-N-acetylglucosaminidase D but resistant to endo-beta-N-acetylglucosaminidase H, and oligosaccharides with the property of 'truncated' precursor oligosaccharides (endoglycosidase-resistant, alpha-mannosidase-sensitive). Endoglycosidase-released oligosaccharides with the properties of hybrid-type structures were derived from the glycoproteins of both transformed and untransformed cells.
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PMID:Both acidic-type and neutral-type asparaginyl-oligosaccharides of host-cell glycoproteins are altered in Rous-sarcoma-virus-transformed chick-embryo fibroblasts. 299 35

Knowledge of the amino acid requirements of a neoplasm is valuable in determining optimal nutritional support and antineoplastic therapy for the tumor-bearing host. The standard human tumor stem cell assay (HTSCA) was modified by reducing an individual amino acid below the normal plasma concentration of the Fischer 344 rat. All other amino acids were maintained at levels sufficient for normal HTSCA tumor colony growth. Twenty-two amino acids were tested at a mean concentration of 12% (range 3% to 35%) of their normal plasma level. Results indicated that all amino acids except L-glutamine and L-asparagine were present in sufficient quantity for normal tumor growth. Dose-response curves have shown more than 70% inhibition of tumor growth with a glutamine concentration of 50% and an asparagine concentration of 25%. Glutamine and asparagine levels of 4% and 1%, respectively, resulted in 100% inhibition. The data indicate that rat sarcoma stem cells are sensitive to decreased glutamine and asparagine concentrations.
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PMID:Amino acid requirements of a rat sarcoma as determined by a stem cell assay. 359 53

Jensen rat sarcoma cells in culture require L-asparagine for growth and lack detectable levels of asparagine synthetase. Cultures exposed for 24 h to graded concentrations of 5-azacytidine give rise to asparagine-independent variants in high frequency. These prototrophs are stable phenotypically whether maintained in the presence or absence of L-asparagine. Asparagine synthetase activity in several variant clones was uniform in thermolability and several kinetic parameters, as well as in immunological properties. Parental Jensen rat sarcoma cells contained no detectable immunologically cross-reacting material. Our data suggest that transitions between asparagine dependence and independence in these cells are mediated by stable shifts in gene expression rather than by structural gene mutations.
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PMID:Properties of asparagine synthetase in asparagine-independent variants of Jensen rat sarcoma cells induced by 5-azacytidine. 619 24


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