Incorporation of deoxyuridine monophosphate into DNA increases the sister-chromatid exchange yield
The effect of a treatment with 5-fluoro-2'-deoxyuridine (FdUrd) in combination with 2'-deoxyuridine (dUrd) on cell proliferation, incorporation of DNA precursors into DNA and sister-chromatid exchanges (SCEs) has been analyzed in Allium cepa meristem cells. FdUrd in the range 10/sup -9/-5 x 10/sup -7/ M produced a dose- and time-dependent decrease in the amount of cells in mitosis. This inhibitory effect could be reversed by 70-80% in short-term (6 h) experiments, by exogenously supplied dUrd at a concentration of 10/sup -1/ M. However, at the highest FdUrd dose tested (10/sup -7/ M), 10/sup -4/ M dUrd could not reverse the FdUrd effect in long-term experiments as shown by analyzing the kinetics of synchronous cell populations. DNA extracted from cells pulsed with (6-/sup 3/H)dUrd in the presence of FdUrd and 6-amino-uracil (6-AU), an inhibitor of uracil-DNA glycosylase, contained a small amount of label in the form of (6-/sup 3/H)dUMP. Thus the authors conclude that under the experimental conditions, exogenously supplied dUrd may be metabolized intracellularly to 2'-deoxyuridine triphosphate (dUTP) and that this deoxynucleotide may eventually be mis-incorporated into DNA. By analyzing SCE levels in third division chromosomes of cells treated with FdUrd and dUrd during their second cycle, they has scored a 6-fold increase in the reciprocal SCE level which demonstrates that the replication of a dUMP-containing DNA template leads to a higher SCE yield.
- Research Organization:
- Universidad de Alcala de Henares, Madrid, Spain
- OSTI ID:
- 6791580
- Journal Information:
- Exp. Cell Res.; (United States), Vol. 168:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ALLIUM CEPA
DNA REPLICATION
DEOXYURIDINE
BIOLOGICAL EFFECTS
FUDR
CELL PROLIFERATION
DNA
DOSE-RESPONSE RELATIONSHIPS
MERISTEMS
MITOSIS
SISTER CHROMATID EXCHANGES
TRITIUM COMPOUNDS
ANTI-INFECTIVE AGENTS
ANTIMETABOLITES
ANTIMICROBIAL AGENTS
AZINES
BODY
CELL DIVISION
CHROMOSOMAL ABERRATIONS
DRUGS
FLUOROURACILS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
MUTATIONS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PLANT TISSUES
PLANTS
PYRIMIDINES
RADIOSENSITIZERS
RIBOSIDES
TISSUES
URACILS
550401* - Genetics- Tracer Techniques