Details

Autor(en) / Beteiligte

• Dahle, D B
• Griffiths, T D
• Carpenter, J G

Titel

Inhibition of Deoxyribonucleic Acid Synthesis and Replicon Elongation in Mammalian Cells Exposed to Methyl Methanesulfonate

Ist Teil von

• Molecular pharmacology, 1978-03, Vol.14 (2), p.278

Ort / Verlag

United States: American Society for Pharmacology and Experimental Therapeutics

Erscheinungsjahr

1978

Quelle

MEDLINE

Beschreibungen/Notizen

• DNA synthesis in Chinese hamster V-79 cells exposed to the alkylating agent methylmethanesulfonate (MMS) was investigated by radioactively labeled thymidine incorporation, followed by Geiger counting, liquid scintillation counting, cell radioautography, and DNA fiber radioautography. Exposure of randomly dividing cells to MMS results in a rapid, dose-dependent decline in the rate of cellular DNA synthesis, followed later by an apparent recovery in the rate of DNA synthesis. The inhibition of DNA synthesis cannot be explained by effects on cell progression or thymidine transport, or by any apparent effects on thymidine metabolism. Analysis of the lengths of labeled segments in DNA fiber radioautograms indicated that MMS significantly decreases either the rate or extent of DNA chain elongation. This inhibition is only temporary, however, since by 6 or 10 hr following treatment with 1 or 3 mM MMS, respectively, the lengths of replication segments return to control values. The degree of inhibition of cellular DNA synthesis following exposure to MMS parallels the inhibition of DNA chain elongation but is quantitatively greater over the entire time course of the experiment. This suggests that exposure to MMS results in constant but protracted inhibition of replicon initiation events. These findings are discussed in terms of the lesions that MMS is known to produce in DNA and their possible relationship to two known mechanisms of inhibition of DNA synthesis.