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Abnormal ultraviolet mutagenic spectrum in plasmid DNA replicated in cultured fibroblasts from a patient with the skin cancer-prone disease, xeroderma pigmentosum

Journal Article · · J. Clin. Invest.; (United States)
DOI:https://doi.org/10.1172/JCI113248· OSTI ID:5650854
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A shuttle vector plasmid, pZ189, was utilized to assess the types of mutations that cells from a patient with xeroderma pigmentosum, complementation group D, introduce into ultraviolet (UV) damaged, replicating DNA. Patients with xeroderma pigmentosum have clinical and cellular UV hypersensitivity, increased frequency of sun-induced skin cancer, and deficient DNA repair. In comparison to UV-treated pZ189 replicated in DNA repair-proficient cells, there were fewer surviving plasmids, a higher frequency of plasmids with mutations, fewer plasmids with two or more mutations in the marker gene, and a new mutagenic hotspot. The major type of base substitution mutation was the G:C to A:T transition with both cell lines. These results, together with similar findings published earlier with cells from a xeroderma pigmentosum patient in complementation group A, suggest that isolated G:C to A:T somatic mutations may be particularly important in generation of human skin cancer by UV radiation.
Research Organization:
National Cancer Institute, Bethesda, MD
OSTI ID:
5650854
Journal Information:
J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 80:6; ISSN JCINA
Country of Publication:
United States
Language:
English

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Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BODY
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DISEASES
DNA
DNA REPLICATION
ELECTROMAGNETIC RADIATION
FIBROBLASTS
MAMMALS
MAN
MUTATIONS
NEOPLASMS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PLASMIDS
PRIMATES
RADIATIONS
RADIOINDUCTION
RADIOSENSITIVITY
SKIN
SKIN DISEASES
SOMATIC CELLS
SOMATIC MUTATIONS
ULTRAVIOLET RADIATION
VERTEBRATES
XERODERMA PIGMENTOSUM