Bromodeoxyuridine mutagenesis in mammalian cells is related to deoxyribonucleotide pool imbalance.

Molecular and Cellular Biology
C R Ashman, R L Davidson

Abstract

The relationship between bromodeoxyuridine (BrdUrd) mutagenesis in mammalian cells and the effects of BrdUrd on deoxyribonucleoside triphosphate pools was analyzed. It was found that the exposure of Syrian hamster melanoma cells to mutagenic concentrations of BrdUrd resulted in the formation of a large bromodeoxyuridine triphosphate (BrdUTP) pool, which remained at a high level for several days. In contrast, the size of the deoxycytidine triphosphate (dCTP) pool dropped rapidly after the addition of BrdUrd, reached a minimum at about 6 h, and then expanded gradually to nearly its original level over the next 3 days. The addition of lower concentrations of BrdUrd, which had less of a mutagenic effect, resulted in the formation of a smaller BrdUTP pool and a slightly smaller drop in the dCTP pool. When a high concentration of deoxycytidine was added at the same time as a normally mutagenic concentration of BrdUrd, the drop in the dCTP pool was prevented, as was BrdUrd mutagenesis. In all of these experiments, mutagenesis was related to the ratio of BrdUTP to dCTP in the cells. In addition, it was shown that mutagenesis occurred primarily during the first 24 h of BrdUrd exposure, when the BrdUTP/dCTP ratio was at its highest level...Continue Reading

References

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Citations

Mar 2, 2012·Nucleic Acids Research·Leonid Schneider, Fabrizio d'Adda di Fagagna
May 1, 1989·Molecular & General Genetics : MGG·R G SargentC K Mathews
Jul 18, 1983·Biochemical and Biophysical Research Communications·C N Newman, J H Miller
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Nov 13, 2008·Cytotechnology·Serkan YılmazHüseyin Aksoy
Jul 1, 1991·Somatic Cell and Molecular Genetics·M T Kresnak, R L Davidson
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Jan 1, 1994·Journal of Neuro-oncology·A FreeseM J O'Connor
May 18, 2013·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Stephan SauerAmar J S Klar
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Jan 1, 1982·Environmental Mutagenesis·B A Kunz
Jan 1, 1983·Pharmacology & Therapeutics·G R Stark, P A Bartlett
Jul 1, 1988·Mutation Research·B A Kunz

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