Caffeine toxicity is inversely related to DNA repair in simian virus 40-transformed xeroderma pigmentosum cells irradiated with ultraviolet light
- Univ. of California, San Francisco (USA)
Human cells transformed by simian virus 40 (SV40) are more sensitive to killing by ultraviolet light when grown in caffeine after irradiation. The degree of sensitization at 2 mM caffeine (expressed as the ratio of the 37% survival dose for control cells divided by the 37% survival dose for cells grown in caffeine, i.e., the dose modification factor) was approximately 1.9 in transformed normal cells and 3.8-5.8 in excision-defective xeroderma pigmentosum (XP) groups A, C, and D cells. A large dose modification factor of 12 was observed in a transformed XP variant cell line. Chinese hamster ovary cells were not significantly different from transformed normal human cells, with a maximum dose modification factor of 1.5. Two radioresistant XP revertants that do not excise cyclobutane dimers gave different responses; one resembled its group A parent in being sensitized by caffeine, and one did not. These results can be interpreted on the basis of a single hypothesis that cells are killed as a result of attempts to replicate damaged DNA. Increased replication rates caused by transformation, increased numbers of replication forks in DNA caused by caffeine, and increased numbers of damaged sites ahead of replication forks in excision-defective cells are all processes that will consequently increase killing according to this hypothesis. A corollary is that the XP variant may be highly sensitized to caffeine because of excision defects at the DNA replication forks, an idea that may be important in designing cloning strategies for the XP variant gene.
- OSTI ID:
- 5467797
- Journal Information:
- Teratogenesis, Carcinogenesis, and Mutagenesis; (USA), Vol. 9:3; ISSN 0270-3211
- Country of Publication:
- United States
- Language:
- English
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CAFFEINE
RADIOSENSITIVITY EFFECTS
CHO CELLS
RADIOSENSITIVITY
XP CELLS
BIOLOGICAL RADIATION EFFECTS
CELL KILLING
DNA REPAIR
DNA REPLICATION
MAN
REVERTANTS
SIMIAN VIRUS
SURVIVAL TIME
ULTRAVIOLET RADIATION
XERODERMA PIGMENTOSUM
ANALEPTICS
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CENTRAL NERVOUS SYSTEM AGENTS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
MAMMALS
MICROORGANISMS
MUTANTS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PARASITES
PRIMATES
PURINES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
SKIN DISEASES
VERTEBRATES
VIRUSES
XANTHINES
560120* - Radiation Effects on Biochemicals
Cells
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