Studies on the relationship between the cancer chemotherapeutic agent, hydroxyurea, and DNA repair in mammalian cells
To examine the possibility that manipulating DNA repair might lessen drug resistance, we investigated whether depletion of the thymidine triphosphate (TTP) pool or administration of hydroxyurea could interfere with the ability of confluent normal human skin fibroblasts to repair ultraviolet irradiation-induced DNA damage. A method was developed for the quantitation of cellular TTP pools by labeling them with (/sup 3/H)thymidine. The addition of hydroxyurea, either simultaneously with (/sup 3/H)thymidine or two hours later, resulted in a dose- and time-dependent increase in the (/sup 3/H)TTP pool. The capacity of these cells to carry out DNA repair was quantitated by their ability to perform repair replication synthesis of DNA after exposure to ultraviolet irradiation. This radiation produces thymine dimers in DNA, which are repaired by the nucleotide excision repair pathway. The experimental protocol resulted in an 8-10-fold reduction in the (/sup 3/H)TTP pool. Saturating levels of DNA repair synthesis were observed under these conditions, with no further diminution of the already reduced (/sup 3/H)TTP pool. Repair replication and (/sup 3/H)TTP pool measurements were identical in cultures treated with 10 mM hydroxyurea and in those not exposed to the drug.
- Research Organization:
- Temple Univ., Philadelphia, PA (USA)
- OSTI ID:
- 6073802
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
59 BASIC BIOLOGICAL SCIENCES
FIBROBLASTS
DNA REPAIR
HYDROXYUREA
RADIOSENSITIVITY EFFECTS
NEOPLASMS
CHEMOTHERAPY
TUMOR CELLS
SENSITIVITY
ANTINEOPLASTIC DRUGS
DOSE-RESPONSE RELATIONSHIPS
GENETIC RADIATION EFFECTS
MAN
PHOSPHATES
SKIN
THYMIDINE
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ULTRAVIOLET RADIATION
AMIDES
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CONNECTIVE TISSUE CELLS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
PRIMATES
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
RIBOSIDES
SOMATIC CELLS
THERAPY
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture
550600 - Medicine
550901 - Pathology- Tracer Techniques