Ultraviolet mutagenesis in a plasmid vector replicated in lymphoid cells from patient with the melanoma-prone disorder dysplastic nevus syndrome

Journal Article · Wed Nov 01 00:00:00 EST 1989 · Cancer Research; (USA)

OSTI ID:5184301

Seetharam, S; Waters, H L; Seidman, M M; Kraemer, K H ^[1]

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1. National Cancer Institute, Bethesda, MD (USA)

The hereditary dysplastic nevus syndrome (DNS) is an autosomal dominant disorder in which affected individuals have increased numbers of dysplastic (premalignant) nevi and a greater than 100-fold increased risk of developing cutaneous melanoma. Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with hereditary DNS have been shown to be hypermutable to UV radiation. To examine the mechanism involved in this UV hypermutability, we used a shuttle vector plasmid, pZ189, which carries a 160-base pair marker gene, supF, and can replicate in human cells. pZ189 was treated with UV radiation and transfected into DNS6BE, a lymphoblastoid cell line from a patient with hereditary DNS. Plasmid survival after UV was similar with the DNS6BE line and with a lymphoblastoid cell line from a normal donor. Plasmid mutation frequency was greater with the DNS line in accord with the DNS cellular hypermutability. Base sequence analysis was performed on 69 mutated plasmids recovered from the DNS line. There were significantly more plasmids with single base substitution mutations (P less than 0.01) in comparison to UV-treated plasmids passed through normal fibroblasts. pZ189 hypermutability and an increased frequency of single base substitutions was previously found with a cell line from a melanoma-prone xeroderma pigmentosum patient. These differences may be related to the increased melanoma susceptibility in both DNS and xeroderma pigmentosum.

• OSTI ID: 5184301
• Journal Information: Cancer Research; (USA), Vol. 49:21; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
GENE MUTATIONS
RADIOINDUCTION
ULTRAVIOLET RADIATION
MUTAGENESIS
BIOLOGICAL MARKERS
DNA
DNA REPLICATION
FIBROBLASTS
GENES
GENETIC RADIATION EFFECTS
LYMPHOCYTES
MAN
MELANOMAS
MUTATION FREQUENCY
PATIENTS
PLASMIDS
XERODERMA PIGMENTOSUM
ANIMAL CELLS
ANIMALS
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BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DISEASES
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
LEUKOCYTES
MAMMALS
MATERIALS
MUTATIONS
NEOPLASMS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PRIMATES
RADIATION EFFECTS
RADIATIONS
SKIN DISEASES
SOMATIC CELLS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture