Specific toxicity of aphidicolin to ultraviolet-irradiated excision proficient human skin fibroblasts
Aphidicolin, a specific inhibitor of the eucaryotic alpha polymerase, has been employed to study the role of this enzyme in repair of potentially lethal damage (PLD) induced by far u.v. (254 nm) radiation in normal and repair defective primary human fibroblasts. There is strong concentration dependent specific toxicity to cells treated with a fluence of 6 Jm-2 of far-u.v. radiation and incubated with aphidicolin for 2 days over the concentration range 0.0025-2.5 micrograms/ml. A similar effect is seen with a xeroderma pigmentosum (XP) variant (excision proficient) strain but there is no specific toxicity to u.v. irradiated excision deficient XP cells of complementation group A. Inactivation of irradiated excision proficient fibroblasts is rapid over the first 6 h of aphidicolin (1 microgram/ml) treatment but the reaction takes 2 days or longer to complete depending on the u.v. dose. These results demonstrate that the apparent uncoupling of excision repair seen previously by other investigators prevents repair of PLD and is lethal to the cells.
- Research Organization:
- Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland
- OSTI ID:
- 5976549
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 4:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BIOLOGICAL REPAIR
INHIBITION
DNA
ANTIBIOTICS
ENZYME INHIBITORS
FIBROBLASTS
POLYMERASES
SKIN
TOXICITY
ULTRAVIOLET RADIATION
XERODERMA PIGMENTOSUM
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
BIOLOGICAL RECOVERY
BODY
CONNECTIVE TISSUE CELLS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
RADIATIONS
RECOVERY
REPAIR
SKIN DISEASES
SOMATIC CELLS
TRANSFERASES
560121* - Radiation Effects on Cells- External Source- (-1987)