Human Molecular Genetics, Vol 5, 215-221, Copyright © 1996 by Oxford University Press
GM Martin, CE Ogburn, LM Colgin, AM Gown, SD Edland and RJ Monnat Jr
We have used a primary cloning assay to determine the frequency of 6-
thioguanine (TG)-resistant tubular epithelial cells in kidney tissue from
72 human donors ranging in age from 2 to 94 years. The frequency of
TG-resistant mutants ranged from approximately 5 x 10(-5) for donors in the
first decade of life to approximately 2.5 x 10(-4) for donors in the eighth
and later decades of life. Two different statistical analyses indicated
that this increase in mutant frequency is exponential with age. We also
observed a 2-fold higher TG-resistant mutant frequency in nephrectomy
kidneys containing a coincident renal carcinoma. DNA sequence analyses
revealed HPRT gene mutations in each of 14 TG-resistant mutants from seven
unrelated donors. Thirteen of these 14 mutants resulted from independent
mutational events. These results suggest that somatic mutations are common
in renal--and perhaps in other human--epithelia, and thus could play an
important role in the genesis of age-associated disease.
ARTICLES
Somatic mutations are frequent and increase with age in human kidney epithelial cells
Department of Pathology, University of Washington, Seattle 98195, USA.
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