Thymidine and uridine metabolism at cell growth inhibition of HeLa cells by human liver extract

Abstract

1. 1. Human liver supernatant contains a cell growth inhibitor that affects the DNA and RNA synthesis of HeLa cells in vitro. Tissue extracts from other species have been reported to contain inhibitors related to arginase. The human liver inhibitor, however, seems to lack arginase activity. 2. 2. The liver supernatant factor inhibits weakly the penetration of different DNA precursors into HeLa cells and inhibits strongly the phosphorylation and incorporation of thymidine into DNA. An increased catabolism of thymidine nucleotides and excretion of thymine into the growth medium is also induced. 3. 3. Cell-free extracts from control and inhibited HeLa cells phosphorylate thymidine at about the same rate, which indicates that the inhibition of thymidine phosphorylation obtained at growth inhibition is a secondary effect. The primary inhibition target may instead be DNA polymerase because extracts from control HeLa cells have a higher DNA polymerase activity than extracts from inhibited cells. 4. 4. The mechanism of RNA synthesis repression was also studied. An impaired phosphorylation of UMP was observed at growth inhibition.