Specific toxicity of aphidicolin to ultraviolet-irradiated excision proficient human skin fibroblasts

Journal Article · Sat Jan 01 04:00:00 EST 1983 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/4.3.327· OSTI ID:5976549

Tyrrell, R M

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), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 4:3; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CONNECTIVE TISSUE CELLS
DISEASES
DNA
DRUGS
ELECTROMAGNETIC RADIATION
ENZYME INHIBITORS
ENZYMES
FIBROBLASTS
INHIBITION
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
RADIATIONS
RECOVERY
REPAIR
SKIN
SKIN DISEASES
SOMATIC CELLS
TOXICITY
TRANSFERASES
ULTRAVIOLET RADIATION
XERODERMA PIGMENTOSUM