scholarly journals The Effect of 6-Mercaptopurine on the Incorporation of Labeled Amino Acids into Cellular Protein of Chronic Granulocytic Leukemia Leukocytes

Blood ◽  
1961 ◽  
Vol 18 (3) ◽  
pp. 336-343 ◽  
Author(s):  
SAMUEL B. NADLER ◽  
HANS J. HANSEN ◽  
CHARLES C. SPRAGUE ◽  
HARRY SHERMAN

Abstract The leukocytes of chronic granulocytic leukemia incorporate labeled valine and leucine at a higher rate than normal leukocytes. 6-mercaptopurine causes significant decrease in the rate of amino acid incorporation into cellular protein of leukemic cells. The onset of a sharp decrease in the amino acid incorporation rate by granulocytic leukemic cells occurs only after several days of therapeutic oral doses of 6-mercaptopurine. The decrease in incorporation rate precedes the decrease in circulating leukocytes by several days, indicating that damage to a vital function of these cells occurs before their disappearance from the blood stream. The decrease in the amino acid incorporation rate persists as long as the leukemia is in remission and even after therapy has been stopped; it exists until exacerbation occurs. Increase in incorporation accompanies exacerbation of the leukemic cell count. A possible action of 6-mercaptopurine is its role in interference with amino acid incorporation into cellular protein of chronic granulocytic leukemia cells.

1967 ◽  
Vol 22 (3) ◽  
pp. 348-351 ◽  
Author(s):  
Gottfried Galling

The amino acid incorporation into protein by cell-free preparations of Chlorella pyrenoidosa is found to be stimulated by DNA isolated from various organisms. This stimulation is not affected by preincubation of the DNA with ribonuclease and by addition of ribonuclease to the reaction mixture. Streptomycin which reduces amino acid incorporation in the normal system stimulates slightly the incorporation in the presence of DNA. The incorporation rate is linearly dependent upon the amount of DNA in the reaction mixture from 10 to 100 µg DNA. Ribosomes from nitrogen-deficient cells exhibit a similar rate of stimulation by DNA. Deoxycholate-treated particles show much higher stimulation by added DNA than normal ribosomes do.


Blood ◽  
1971 ◽  
Vol 38 (5) ◽  
pp. 638-647 ◽  
Author(s):  
N. V. DIMITROV ◽  
J. HANSZ ◽  
M. A. TOTH ◽  
B. BARTOLOTTA

Abstract Leukocytes from patients with acute granulocytic leukemia (AGL), acute monocytic leukemia (AMoL) and blastic crisis of chronic granulocytic leukemia (BC) were incubated with serine-U-C14 or aspartic acid-U-C14. The metabolism was followed by determination of radioactivity of CO2, lipids, proteins, organic acids, and nucleotides. Leukemic leukocytes in AGL, AMoL, and BC exhibit high serine utilization compared to lymphocytic leukemias. Significant changes in the metabolic pattern of the leukocytes from patients with chronic granulocytic leukemia (CGL) preceded the onset of blastic crisis. Serine utilization remained abnormal in two patients with AGL after complete remission was achieved. Low conversion of serine to CO2 in AMoL was associated with achievement of complete remission and long survival time. Aspartic acid was most actively metabolized by leukemic cells in BC. The results of these studies indicate that the metabolic pattern of serine and aspartic acid varies with the type of leukemic cell. There is evidence that mature polymorphonuclear (PMN) leukocytes in the blood of leukemic patients may possess an abnormal metabolism.


Blood ◽  
1960 ◽  
Vol 16 (5) ◽  
pp. 1555-1563 ◽  
Author(s):  
FELICE GAVOSTO ◽  
GIOVANNI MARAINI ◽  
ALESSANDRO PILERI

Abstract DNA, RNA and protein metabolism was investigated by means of a high resolution autoradiographic technic in normal and acute leukemia blast cells by studying the incorporation of tritiated thymidine, uridine, leucine and phenylalanine. A strikingly lower percentage of cells labelled with thymidine was demonstrated in acute leukemia and was interpreted as evidence of a decreased proliferative capacity. A very significantly lower uptake of uridine, leucine and phenylalanine was detected in acute leukemia cells. In normal and leukemic cells, amino acid incorporation occurred both in the nucleus and in the cytoplasm; uridine was incorporated exclusively in the nucleus during the first hour of incubation and the cytoplasm became labelled only in a later period. The constant ratio between uridine and amino acid incorporation detected in normal myeloblasts was always altered in acute leukemia cells. The lower RNA and protein metabolism and its dissociation in acute leukemia cells was discussed as related to the well-known maturation defect of these cells.


Amino Acids ◽  
2020 ◽  
Author(s):  
Thomas L. Williams ◽  
Debra J. Iskandar ◽  
Alexander R. Nödling ◽  
Yurong Tan ◽  
Louis Y. P. Luk ◽  
...  

AbstractGenetic code expansion is a powerful technique for site-specific incorporation of an unnatural amino acid into a protein of interest. This technique relies on an orthogonal aminoacyl-tRNA synthetase/tRNA pair and has enabled incorporation of over 100 different unnatural amino acids into ribosomally synthesized proteins in cells. Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA from Methanosarcina species are arguably the most widely used orthogonal pair. Here, we investigated whether beneficial effect in unnatural amino acid incorporation caused by N-terminal mutations in PylRS of one species is transferable to PylRS of another species. It was shown that conserved mutations on the N-terminal domain of MmPylRS improved the unnatural amino acid incorporation efficiency up to five folds. As MbPylRS shares high sequence identity to MmPylRS, and the two homologs are often used interchangeably, we examined incorporation of five unnatural amino acids by four MbPylRS variants at two temperatures. Our results indicate that the beneficial N-terminal mutations in MmPylRS did not improve unnatural amino acid incorporation efficiency by MbPylRS. Knowledge from this work contributes to our understanding of PylRS homologs which are needed to improve the technique of genetic code expansion in the future.


1955 ◽  
Vol 215 (1) ◽  
pp. 111-124 ◽  
Author(s):  
Henry Borsook ◽  
Adolph Abrams ◽  
Peter H. Lowy

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