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 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.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000302:isolation & purification; D004261:DNA Replication / Q000187:drug effects*; D014644:Genetic Variation; D007700:Kinetics; D008168:Lung; D008466:Mechlorethamine / Q000633:toxicity*; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D008970:Molecular Weight
D008466:Mechlorethamine; D004247:DNA; D008741:Methyl Methanesulfonate