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

A u.v. sensitive Chinese hamster cell line V79/79 has been shownto 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 onDNA synthesis measured by [³H]thymidine (TdR) incorporationinto whole cells and by alkaline sucrose gradient sedimentation¹⁴C-labelled template and of pulse labelled DNA revealed nosignificant differences between the responses of the two celllines. The effects of a range of doses of both drugs on therate of progress through the cell cycle was compared using cytofluorimetry.The more sensitive V79/79 cells failed to show a significantdelay in progress through the cell cycle even at the highestdoses tested (0.2 µM HN2 and 2.0 mM MMS). In contrast,V79 cells showed a marked S phase delay in response to bothHN2 and MMS exposure. The possible relationships between failureto delay cell cycle progression, and cellular sensivity arediscussed.