Caffeine toxicity is inversely related to DNA repair in simian virus 40-transformed xeroderma pigmentosum cells irradiated with ultraviolet light

Journal Article · Sat Dec 31 23:00:00 EST 1988 · Teratogenesis, Carcinogenesis, and Mutagenesis; (USA)

DOI:https://doi.org/10.1002/tcm.1770090303· OSTI ID:5467797

Cleaver, J E ^[1]

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1. 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), Journal Name: Teratogenesis, Carcinogenesis, and Mutagenesis; (USA) Vol. 9:3; ISSN TCMUD; ISSN 0270-3211
• Country of Publication: United States
• Language: English

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560120* -- Radiation Effects on Biochemicals
Cells
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANALEPTICS
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CAFFEINE
CELL KILLING
CENTRAL NERVOUS SYSTEM AGENTS
CHO CELLS
DISEASES
DNA REPAIR
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
MAMMALS
MAN
MICROORGANISMS
MUTANTS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PARASITES
PRIMATES
PURINES
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RECOVERY
REPAIR
REVERTANTS
SIMIAN VIRUS
SKIN DISEASES
SURVIVAL TIME
ULTRAVIOLET RADIATION
VERTEBRATES
VIRUSES
XANTHINES
XERODERMA PIGMENTOSUM
XP CELLS