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PMID: 6942420 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Elevated spontaneous mutation rate in Bloom syndrome fibroblasts.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 78 ·No. 5 ·1981-05-00 ·Pages 3133-7

Warren ST, Schultz RA, Chang CC, Wade MH, Trosko JE

Abstract

The rates of spontaneous mutation to 6-thioguanine resistance were determined in fibroblasts derived from normal and two Bloom syndrome individuals (GM 2548 and GM 1492). Two methods were utilized to determine the rates. Method I obtained the spontaneous mutation rate from the increase in the mutation frequency of a cell population in logarithmic-phase growth over 10 days. The two Bloom syndrome strains had spontaneous mutation rates of 16 X 10(-6) and 17 X 10(-6) mutations per cell per generation, whereas two normal strains had rates of 1.5 X 10(-6) and 1.1 X 10(-6). Method II utilized fluctuation analysis to measure the rate of spontaneous mutation. This method resulted in rates of 19 X 10(-6) and 23 X 10(-6) mutations per cell per generation in Bloom syndrome cells, compared to rates of 4.6 X 10(-6) and 4.9 X 10(-6) in the control strains. These data suggest that Bloom syndrome may be a mutator mutation, a previously unrecognized phenomenon in humans, and that an elevated spontaneous mutation rate in vivo may be responsible for the clinical phenotype of primordial dwarfism and increased cancer incidence.

MeSH Terms
Abnormalities, Multiple/genetics Cell Division Cell Line Fibroblasts/physiology Humans Kinetics Mutation Skin/physiopathology Syndrome Telangiectasis/genetics
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Warren S T
Schultz R A
Chang C C
Wade M H
Trosko J E
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41 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.78.5.3133
Published
1981-05-00
Pages
3133-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC319514
Subset
IM
Grants
NCI NIH HHS · 1 P01 CA 26803 · United States
NIEHS NIH HHS · ES01809 · United States
External Links
PubMed source DOI: 10.1073/pnas.78.5.3133 PMC Full Text View journal details
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