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INHIBITION OF PROTEIN SYNTHESIS IN HUMAN LYMPHOCYTES BY THIOPURINES
Author(s) -
Smith JL,
Forbes IJ
Publication year - 1970
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1970.28
Subject(s) - phytohaemagglutinin , azathioprine , mercaptopurine , chemistry , in vitro , pharmacology , biochemistry , biology , microbiology and biotechnology , medicine , disease
Summary Azathioprine, 6‐mercaptopurine and 6‐thioguanine inhibited synthesis of protein by human peripheral lymphocytes in vitro. Maximum inhibition occurred at concentration of about 60 μg./ml., whereas the blood concentrations do not exceed 2 μg./ml. Azathioprine was generally as inhibitory as 6‐mercaptopurine, or more inhibitory, at half the molar concentration. Azathioprine caused an accelerated rate of death from 12 to 24 hrs. in vitro not seen in cells incubated with 6‐mertaptopurine and 6‐thioguanine. These data correlate with greater effectiveness of azathioprine in suppressing immune responses in animals. The effect of plasma on the inhibition caused by thiopurines was variable. The degree of inhibition was generally of the same order in the presence of phytohaemagglutinin. Azathioprine suppressed phytohaemagglutinin‐stimulated lymphocytes more than 6‐mercaptopurine. 2‐Hydroxy‐6‐mercaptopurine, 6‐mercaptopurine ribonucleoside, 6‐thiouric acid and 5‐mercapto‐1‐methyl‐4‐nitroimidazole (ammonium salt) caused little or no inhibition of protein synthesis by human lymphocytes. 6‐Mercaptopurine ribonucleoside and 6‐mercaptopurine ribonucleotide caused inhibition of protein synthesis by lymphocytes. The pronounced inhibition of protein synthesis by the thiopurines contransted with smaller and less constant inhibition of incorporation of radioactive precursors into ribonucleic acid.

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