The role of suppression of DNA synthesis and inhibition of cell cycle progression in cellular sensitivity to alkylation damage.

Abstract

A u.v. sensitive Chinese hamster cell line V79/79 has been shown to be also more sensitive to methyl methanesulphonate (MMS) and nitrogen mustard (HN2) exposure than wild-type V79 cells. A comparison of the effects of the two alkylating agents on DNA synthesis measured by [3H]thymidine (TdR) incorporation into whole cells and by alkaline sucrose gradient sedimentation 14C-labelled template and of pulse labelled DNA revealed no significant differences between the responses of the two cell lines. The effects of a range of doses of both drugs on the rate of progress through the cell cycle was compared using cytofluorimetry. The more sensitive V79/79 cells failed to show a significant delay in progress through the cell cycle even at the highest doses tested (0.2 microM HN2 and 2.0 mM MMS). In contrast, V79 cells showed a marked S phase delay in response to both HN2 and MMS exposure. The possible relationships between failure to delay cell cycle progression, and cellular sensitivity are discussed.