Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F

Journal Article · Sat Jun 15 00:00:00 EDT 1991 · Cancer Research; (United States)

OSTI ID:5264992

Yagi, T; Tatsumi-Miyajima, J; Sato, M; Kraemer, K H; Takebe, H ^[1]

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1. Kyoto Univ. (Japan)

To assess the contribution to mutagenesis by human DNA repair defects, a UV-treated shuttle vector plasmid, pZ189, was passed through fibroblasts derived from Japanese xeroderma pigmentosum (XP) patients in two different DNA repair complementation groups (A and F). Patients with XP have clinical and cellular UV hypersensitivity, increased frequency of skin cancer, and defects in DNA repair. The XP DNA repair defects represented by complementation groups A (XP-A) and F (XP-F) are more common in Japan than in Europe or the United States. In comparison to results with DNA repair-proficient human cells (W138-VA13), UV-treated pZ189 passed through the XP-A (XP2OS(SV)) or XP-F (XP2YO(SV)) cells showed fewer surviving plasmids (XP-A less than XP-F) and a higher frequency of mutated plasmids (XP-A greater than XP-F). Base sequence analysis of more than 200 mutated plasmids showed the major type of base substitution mutation to be the G:C----A:T transition with all three cell lines. The XP-A and XP-F cells revealed a higher frequency of G:C----A:T transitions and a lower frequency of transversions among plasmids with single or tandem mutations and a lower frequency of plasmids with multiple point mutations compared to the normal line. The spectrum of mutations in pZ189 with the XP-A cells was similar to that with the XP-F cells. Seventy-six to 91% of the single base substitution mutations occurred at G:C base pairs in which the 5{prime}-neighboring base of the cytosine was thymine or cytosine. These studies indicate that the DNA repair defects in Japanese XP patients in complementation groups A and F result in different frequencies of plasmid survival and mutagenesis but in similar types of mutagenic abnormalities despite marked differences in clinical features.

• OSTI ID: 5264992
• Journal Information: Cancer Research; (United States), Vol. 51:12; 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.
MUTATIONS
RADIOINDUCTION
XP CELLS
DNA REPAIR
DNA REPLICATION
FIBROBLASTS
MUTAGENESIS
MUTATION FREQUENCY
PATIENTS
PLASMIDS
SKIN
ULTRAVIOLET RADIATION
XERODERMA PIGMENTOSUM
ANIMAL CELLS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DISEASES
ELECTROMAGNETIC RADIATION
NUCLEIC ACID REPLICATION
ORGANS
RADIATIONS
RECOVERY
REPAIR
SKIN DISEASES
SOMATIC CELLS
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture