Oxygen Dependent Regulation of DNA Replication of Ehrlich Ascites Cells In Vitro and In Vivo

Abstract

Control of cell growth in higher animals normally occurs by switching between a resting and a cycling state. In most cases resting occurs at 2 c DNA content (G0 phase). The metabolism of resting cells is organized principally different to that of cycling cells, which generally are committed to DNA synthesis. When resting cells receive a switching signal, they usually require several hours before they can enter DNA synthesis. It is commonly believed that DNA synthesis, once started, proceeds relatively autonomously following a more or less fixed S-phase program [1] which typically runs for 5–8 h. This program temporally and spatially organizes the activation of groups (clusters) of replication units (replicons) [1]. Different sets of clusters are activated at different times in the S phase. The sets are thought to comprise functionally related genes [2]. In cycling cells, the synthesis of DNA and of DNA-associated protein occupies a considerable portion of total metabolic activity. This concerns both the consumption of organic matter as well as of ATP energy. The present paper deals with an oxygen-dependent regulation system acting by selectively suppressing or re-triggering activation of replicon clusters in Ehrlich ascites cells. The regulation sets in before hypoxia imposes measurable metabolic constraints to the cells.

Dedicated to Prof. Dr. Fr. Schneider on the occasion of his 60th birthday