Biological effects of pyrimidine (6-4)pyrimidone photoproducts in UV-irradiated mammalian cells

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:6694838

Mitchell, D L

Radioimmunoassays were used to analyze the repair of (6-4) photoproducts in various human and rodent cell lines displaying diverse UV-sensitivities and excision repair capacities. From these studies a correlation is described between (6-4) photoproduct removal and early events associated with excision repair. Using host cell reactivation, transient gene expression in transfected normal and repair-deficient CHO mutant cell lines was shown to be inhibited by both (6-4) photoproducts and cyclobutane dimers. A new radioimmunoassay was developed which specifically detects the photoisomerization product of the (6-4) photoproduct in DNA. This assay was used to further characterize the photochemistry and photobiology of the (6-4) photoproduct and its photoisomer; including the rate and wavelength-dependence of photoisomerization, as well as the repair of this secondary photoproduct in various normal and UV-hypersensitive human cell lines. Antibody-binding experiments confirmed indirect data regarding the alkali-lability of the (6-4) photoisomer and led to the establishment of conditions which resulted in DNA strand-breakage at this site. Using these data, a procedure was developed to directly quantify (6-4) photoproducts in DNA irradiated with low UV fluences. (6-4) photoproducts were subsequently determined as photo-induced alkalilabile sites in DNA.

• Research Organization: Texas Univ., Austin, TX (USA)
• OSTI ID: 6694838
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AZINES
BIOASSAY
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHO CELLS
DIAGNOSTIC TECHNIQUES
DNA REPAIR
ELECTROMAGNETIC RADIATION
EXCISION REPAIR
GENE REGULATION
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
HETEROCYCLIC COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
MAMMALS
MAN
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RADIOINDUCTION
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
STRAND BREAKS
TRACER TECHNIQUES
ULTRAVIOLET RADIATION
VERTEBRATES