scholarly journals Inhibition of DNA Synthesis and Mitosis by DNA Affinity Proteins Released from Thymus Cells during in Vitro Incubation

1979 ◽  
Vol 4 (4) ◽  
pp. 275-284
Author(s):  
Shohei Miyata ◽  
Hirozi K. Kihara
1966 ◽  
Vol 44 (6) ◽  
pp. 839-852 ◽  
Author(s):  
D. K. Myers ◽  
Kirsten Skov

The rate of incorporation of thymidine into the deoxyribonucleic acid (DNA) of rat thymocytes in vitro was not immediately affected by low doses of X-radiation, but became progressively more inhibited as the irradiated cells were incubated at 37 °C for periods of up to 6 hours. Ribonucleic acid (RNA) synthesis deteriorated almost at the same rate as DNA synthesis after X-irradiation in vitro, but protein synthesis was slightly more resistant. Addition of 10–50 mM nicotinamide to the irradiated cell suspensions tended to retard the development of this inhibition, particularly at low temperatures, but high concentrations of nicotinamide were also toxic to these cells. The inhibition of DNA synthesis by X-irradiation appeared to follow a qualitatively similar pattern in thymus, spleen, and regenerating liver in vivo.In addition to the inhibition resulting from degenerative processes in the irradiated cells, DNA synthesis in vitro was directly inhibited by 20–30 kr X-radiation. The effects of radiation on DNA synthesis paralleled to some extent its effects on the gel-forming capacity of the deoxyribonucleoprotein from the thymus cells. It is suggested that the normal synthesis of both RNA and DNA in thymocytes depends on the integrity of the deoxyribonucleoprotein.


1985 ◽  
Vol 21 (11) ◽  
pp. 1325-1330 ◽  
Author(s):  
G. Leyhausen ◽  
H.C. Schröder ◽  
D.K. Schuster ◽  
A. Maidhof ◽  
H. Umezawa ◽  
...  

Nature ◽  
1979 ◽  
Vol 279 (5708) ◽  
pp. 75-78 ◽  
Author(s):  
HIROSHI MIZUSAWA ◽  
TSUYOSHI KAKEFUDA

1969 ◽  
Vol 113 (3) ◽  
pp. 515-524 ◽  
Author(s):  
T J Franklin ◽  
Jennifer M. Cook

1. Mycophenolic acid, an antibiotic of some antiquity that more recently has been found to have marked activity against a range of tumours in mice and rats, strongly inhibits DNA synthesis in the L strain of fibroblasts in vitro. 2. The extent of the inhibition of DNA synthesis is markedly increased by preincubation of the cells with mycophenolic acid before the addition of [14C]thymidine. 3. The inhibition of DNA synthesis by mycophenolic acid in L cells in vitro is reversed by guanine in a non-competitive manner, but not by hypoxanthine, xanthine or adenine. 4. The reversal of inhibition by guanine can be suppressed by hypoxanthine, 6-mercaptopurine and adenine. 5. Mycophenolic acid does not inhibit the incorporation of [14C]thymidine into DNA in suspensions of Landschütz and Yoshida ascites cells in vitro. 6. Mycophenolic acid inhibits the conversion of [14C]hypoxanthine into cold-acid-soluble and -insoluble guanine nucleotides in Landschütz and Yoshida ascites cells and also in L cells in vitro. There is some increase in the radioactivity of the adenine fraction in the presence of the antibiotic. 7. Mycophenolic acid inhibits the conversion of [14C]hypoxanthine into xanthine and guanine fractions in a cell-free system from Landschütz cells capable of converting hypoxanthine into IMP, XMP and GMP. 8. Preparations of IMP dehydrogenase from Landschütz ascites cells, calf thymus and LS cells are strongly inhibited by mycophenolic acid. The inhibition showed mixed type kinetics with Ki values of between 3·03×10−8 and 4·5×10−8m. 9. Evidence was also obtained for a partial, possibly indirect, inhibition by mycophenolic acid of an early stage of biosynthesis of purine nucleotides as indicated by a decrease in the accumulation of formylglycine amide ribonucleotide induced by the antibiotic azaserine in suspensions of Landschütz and Yoshida ascites cells and L cells in vitro.


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