Inhibition of deoxyribonucleic acid synthesis and replicon elongation in mammalian cells exposed to methyl methanesulfonate

Journal Article · Sun Jan 01 04:00:00 EST 1978 · Mol. Pharmacol.; (United States)

OSTI ID:5884167

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

DNA synthesis in Chinese hamster V-79 cells exposed to the alkylating agent methyl methanesulfonate (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 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.

• Research Organization: Univ. of Rochester, NY
• OSTI ID: 5884167
• Journal Information: Mol. Pharmacol.; (United States), Journal Name: Mol. Pharmacol.; (United States) Vol. 14; ISSN MOPMA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTORADIOGRAPHY
AZINES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
DNA
DOSE-RESPONSE RELATIONSHIPS
ESTERS
HAMSTERS
HETEROCYCLIC COMPOUNDS
INHIBITION
MAMMALS
METHYL METHANESULFONATE
MUTAGENS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PYRIMIDINES
RIBOSIDES
RODENTS
SULFONIC ACID ESTERS
SYNTHESIS
THYMIDINE
VERTEBRATES