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Studies on the relationship between the cancer chemotherapeutic agent, hydroxyurea, and DNA repair in mammalian cells

Thesis/Dissertation ·
OSTI ID:6073802
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
Country of Publication:
United States
Language:
English

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Related Subjects

550600 -- Medicine
550901 -- Pathology-- Tracer Techniques
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CHEMOTHERAPY
CONNECTIVE TISSUE CELLS
DISEASES
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROMAGNETIC RADIATION
FIBROBLASTS
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYDROXYUREA
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MAN
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHORUS COMPOUNDS
PRIMATES
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
RIBOSIDES
SENSITIVITY
SKIN
SOMATIC CELLS
THERAPY
THYMIDINE
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
ULTRAVIOLET RADIATION
VERTEBRATES