The effects of bifunctional alkylating agents on DNA synthesis in sensitive and resistant Yoshida cells.

Abstract

The effects of the alkylating agents methylene dimethanesulphonate (MDMS), sulphur mustard (SM) and methyl methanesulphonate (MMS) on DNA synthesis have been investigated in Yoshida sarcoma cell lines sensitive (YS) and resistant (YR) to these agents. Measurement of overall DNA synthesis by [3H]thymidine uptake into DNA indicated that both MDMS and SM, but not MMS, induced a greater depression of DNA synthesis in YS cells than in YR cells. Analysis of the sizes of newly synthesised strands of DNA by pulse labelling and alkaline sucrose gradient sedimentation revealed that MDMS inhibited the initation of new replicons and also reduced the size of new DNA strands. The relative extents of inhibition of replicon initation in MDMS-treated YS and YR cells were similar and reduced by caffeine while YR cells were comparatively less sensitive to the effect of MDMS on the sizes of DNA molecules synthesised. Similarly, YR cells apparently synthesised longer DNA strands following SM treatment compared to YS cells suggesting an association between the size of DNA molecules synthesized and the sensitivity of Yoshida cells to bifunctional alkylating agents.