The role of suppression of DNA synthesis and inhibition of cell cycle progression in cellular sensitivity to alkylation damage.
AffiliationPaterson Laboratories, Christie Hospital and Holt Radium Institute, Withington, Manchester M20 9BX
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AbstractA 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.
CitationThe role of suppression of DNA synthesis and inhibition of cell cycle progression in cellular sensitivity to alkylation damage. 1983, 4 (3):269-74 Carcinogenesis
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