The Induction of Alkali Labile Sites in DNA of CHO Cells by Methyl Methan-Sulphonate and Dimethylsulfate and Its Relationship to the Inhibition of of Nascent DNA Chain Elongation

Abstract

The induction and repair of alkali labile sites (ALS) with methyl methane sulphonate (MMS) and dimethyl sulphate (DMS) in the DNA of Chinese hamster ovary (CHO) cells is biphasic. During the treatment of cell and early afterwards ALS are induced in DNA; they are removed from DNA by a repair mechanism with a half-life of about 3 hours. Between the 3rd and 6th hour after treatment, secondary ALS developed the repair of which had a half-life of 9 to 16 hours. On treatment of cells, most probably both ALS and potential ALS (PALS) develop; between the 3rd and 6th hour after treatment they are either spontaneously of enzymatically converted to secondary ALS. With smaller doses of MMS (2mM) the secondary ALS do not occur. It seems that as long as the total amount of induced PALS is small, CHO cells possess a sufficient capacity to remove them from DNA already prior to their conversion to ALS. A substantial part of primary and secondary ALS is removed from DNA by a long type of repair sensitive to araC and novobiocin (NB). Secondarily developed ALS are effective blockers of elongation of the nascent DNA chains.