Somatic mosaicism for DNA repair capacity in fibroblasts derived from a group A xeroderma pigmentosum patient

Journal Article · Sun Oct 01 00:00:00 EDT 1989 · Journal of Investigative Dermatology; (USA)

DOI:https://doi.org/10.1111/1523-1747.ep12284030· OSTI ID:5467697

Chang, H R; Ishizaki, K; Sasaki, M S; Toguchida, J; Kato, M; Nakamura, Y; Kawamura, S; Moriguchi, T; Ikenaga, M ^[1]

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1. Kyoto Univ. (Japan)

A female Japanese xeroderma pigmentosum (XP) patient with severe skin lesions and various neurologic abnormalities was assigned to complementation group A by conventional cell fusion studies. Ultraviolet (UV)-irradiated skin fibroblasts showed a biphasic survival curve, as measured by colony-forming ability. The surviving fraction decreased rapidly up to 2 J/m2 of UV, with a steep slope of D(O) (mean lethal dose) = 0.95 J/m2. At much higher doses it decreased more slowly, with D(O) = 3.5 J/m2. To elucidate the cause of this unique survival response, we isolated a large number of independent clones from single colonies and measured their responses to UV. Of 81 clones analyzed, ten showed a marked resistance to killing by UV, which was only slightly more sensitive than normal cells, and these clones had a rate of unscheduled DNA synthesis (UDS) that was about 45% of normal cells. By contrast, the remaining 71 clones were extremely sensitive to UV, typical of XP group A strains, and had a UDS level 1%-3% of normals. Analysis of restriction fragment length polymorphism using seven polymorphic DNA probes indicated that the UV-resistant clones were derived from the same individual as the UV-sensitive clones. These results clearly demonstrate that this patient's fibroblast cells consist of two types with differing responses to UV, and provide direct evidence of somatic mosaicism for DNA repair capacity in an XP patient.

• OSTI ID: 5467697
• Journal Information: Journal of Investigative Dermatology; (USA), Vol. 93:4; ISSN 0022-202X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CLONE CELLS
RADIOSENSITIVITY
FIBROBLASTS
DNA REPAIR
COLONY FORMATION
DNA
FEMALES
MAN
PATIENTS
SKIN DISEASES
SURVIVAL TIME
ULTRAVIOLET RADIATION
XERODERMA PIGMENTOSUM
ANIMAL CELLS
ANIMALS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL CULTURES
CONNECTIVE TISSUE CELLS
DISEASES
ELECTROMAGNETIC RADIATION
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PRIMATES
RADIATIONS
RECOVERY
REPAIR
SOMATIC CELLS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture