Dependence of u. v. -induced DNA excision repair on deoxyribonucleoside triphosphate concentrations in permeable human fibroblasts: a model for the inhibition of repair by hydroxyurea
We have tested the hypothesis that the inhibition by hydroxyurea of repair patch ligation and chromatin rearrangement during u.v.-induced DNA excision repair results from a reduction in cellular deoxyribonucleotide concentrations and not from a direct effect of hydroxyurea on the repair process. Using permeable human fibroblasts, we have shown that hydroxyurea has no direct effect on either repair synthesis or repair patch ligation. We also have shown that by reducing the deoxyribonucleoside triphosphate concentrations in the permeable cell reaction mixture, we can mimic the inhibition of repair patch ligation and chromatin rearrangement seen when u.v.-damaged intact confluent fibroblasts are treated with hydroxyurea. Our results are consistent with the concept that hydroxyurea inhibits DNA repair in intact cells by inhibiting deoxyribonucleotide synthesis through its effect on ribonucleotide reductase and, conversely, that continued deoxyribonucleotide synthesis is required for the excision repair of u.v.-induced DNA damage even in resting cells.
- Research Organization:
- Univ. of Alberta, Edmonton, Canada
- OSTI ID:
- 6169175
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 10
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
FIBROBLASTS
EXCISION REPAIR
GENETIC RADIATION EFFECTS
HYDROXYUREA
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
CELL CULTURES
DNA
OXIDOREDUCTASES
PERMEABILITY
ULTRAVIOLET RADIATION
AMIDES
ANIMAL CELLS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CONNECTIVE TISSUE CELLS
DNA REPAIR
ELECTROMAGNETIC RADIATION
ENZYMES
GENETIC EFFECTS
HYDROXY COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
SOMATIC CELLS
560121* - Radiation Effects on Cells- External Source- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)