Evidence for the inactivation and repair of the mammalian DNA template after alkylation by mustard gas and half mustard gas

Abstract

1. Mustard gas or half mustard gas caused a rapid dose-dependent depression of DNA synthesis in HeLa cells. 2. Synchronous populations of HeLa cells treated prior to DNA synthesis in the G 1 phase of the cell cycle were not delayed in their progression into the S phase, but showed a dose-dependent inhibition of DNA synthesis when the cells entered the S phase. 3. Treatment during the S phase also resulted in a dose-dependent depression in the rate of DNA synthesis. 4. Cells in which the rate of DNA synthesis had been depressed exhibited a prolongation of the S phase and a corresponding mitotic delay. 5. Treatment early in G 1 produced less inhibition of DNA synthesis than treatment late in G 1 probably due to repair of DNA damage before its effects were manifest during the S phase. 6. The different effects on survival of treatment throughout the cell cycle were consistent with this possibility. 7. After cells passed through a mitotic block their subsequent progression was not impaired. 8. Treatment in G 2 did not delay the following mitosis but did induce inhibition of NDA synthesis during the next cell cycle and then mitotic delay. 9. The results accord with the view that the cytotoxic action of these agents was due to the direct inactivation of the DNA template which could, however, be repaired.