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
- 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), Journal Name: Cancer Research; (United States) Vol. 51:12; ISSN 0008-5472; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DISEASES
DNA REPAIR
DNA REPLICATION
ELECTROMAGNETIC RADIATION
FIBROBLASTS
MUTAGENESIS
MUTATION FREQUENCY
MUTATIONS
NUCLEIC ACID REPLICATION
ORGANS
PATIENTS
PLASMIDS
RADIATIONS
RADIOINDUCTION
RECOVERY
REPAIR
SKIN
SKIN DISEASES
SOMATIC CELLS
ULTRAVIOLET RADIATION
XERODERMA PIGMENTOSUM
XP CELLS