Fluctuation of a Cancer-associated Lactate Dehydrogenase during S Phase of the Cell Cycle in HeLa Cells1

An unusual ¡sozymeof lactate dehydrogenase, originally de tected in Kirsten sarcoma virus-infected cells and later shown to be induced in normal mammalian cells by anaerobic shock, has also been reported at elevated levels in several human carcino mas. This enzyme is subject to inhibition by guanosine triphosphate and by the dinucleosides 5',5'"-diadenosine tetraphosphate and 5',5'"-diguanosine tetraphosphate (4). Fluctuation of the activity of this enzyme in soluble extracts of synchronized HeLa cells suggests the enzyme may be linked to DNA synthesis. The lactate dehydrogenase K activity increased in early S phase and then decreased to nearly undetectable levels during the period of most active DNA synthesis. This was observed in cells synchronized by thymidine excess or by aphidicolin, an inhibitor of DNA polymerase a.