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To characterize the nature of multiple mutations in the tissues of an intact animal, the Big Blue transgenic mouse mutation detection system was used to examine 1459 mutants from eight normal tissues and 507 mutants from 11 tumors. Multiple mutations occurred and predominantly doublet mutants were identified (i.e. two mutations within one mutant lacI gene), but multiplets of up to five mutations were observed. The frequency of doublets in normal tissues and spontaneous tumors from p53-deficient mice was enhanced to the same degree (660 and 667 fold, respectively) over that expected for two independent mutational events. Doublets, multiplets and singlets have similar patterns of mutation. The distance between mutations in doublets fits an exponential distribution, not that expected for randomly spaced events, suggesting that many doublets occur in rapid succession within the same cell cycle.
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
May 1998,
Mutation research,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
December 2001,
Mutation research,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
January 1996,
Environmental and molecular mutagenesis,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
July 1999,
Carcinogenesis,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
June 1993,
Mutation research,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
September 2006,
Mutagenesis,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
January 2000,
Environmental and molecular mutagenesis,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
January 2000,
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
September 2001,
Mutation research,
V L Buettner, and
K A Hill, and
W A Scaringe, and
S S Sommer
July 1996,
Mutation research,
