EFFECTS OF 6-THIOGUANINE ON MACROMOLECULAR EVENTS IN REGENERATING RAT-LIVER

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (6) , 1868-1875
Abstract
Regenerating rat liver was used as a semisynchronous system in which to investigate the effects of the antitumor agent 6-thioguanine on biochemical processes occurring in discrete phases of the cell cycle. 6-Thioguanine inhibited the 1st wave of DNA biosynthesis in regenerating rat liver. This effect appeared to be the result of a decrease, caused by 6-thioguanine, in the induction of several enzyme activities (i.e., thymidine kinase, deoxycytidylate deaminase, CDP reductase and DNA polymerase) necessary for the initiation of DNA replication in regenerating liver. There was a fairly short period during which 6-thioguanine could be given to rats to accomplish the inhibition of the appearance of the induced activities of these enzymes. This period corresponded to the time just before enzyme induction. The inhibition of the induced synthesis of this group of enzymes occurred in the presence of an intact translational apparatus and intact polysomes and in the absence of interference with the incorporation of radioactive leucine and tyrosine into total protein of liver. Synthesis of polyadenylate containing RNA was depressed in 6-thioguanine treated rats, whereas the synthesis of polyadenylate lacking RNA was unaffected. The inhibition of the synthesis of polyadenylate containing RNA by 6-thioguanine is at least partly responsible for the observed decrease in induced enzyme activities and the resulting interference with DNA replication.

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