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Oncogenic Base Substitution Mutations in Circulating Leukocytes of Normal Individuals¹

Institute of Environmental Studies [V. L. W., X. Y., B. T., K. R. W., J. P. W.] and Institute for Mutagenesis and the Department of Biological Sciences [V. L. W., X. Y., B. T., K. R. W., J. P. W., W. R. L.], Louisiana State University, Baton Rouge, Louisiana 70803, and The Children’s Hospital, Denver, Colorado 80516 [Q. W.]

The background frequency of mutations in human tissues is an important issue in cancer susceptibility and genotoxic exposure determinations. Here we report the detection of rare mutant leukocytes containing oncogenic base substitutions of the Harvey-ras, N-ras, and p53 genes by the Needle-in-a-Haystack mutation assay with a sensitivity of one cell in a million. Altogether, we detected and identified 17 independent mutations of 66 separate base site analyses of peripheral blood specimens obtained from 19 apparently normal individuals. Two individuals harbored a substantially increased frequency of mutant cells, representing 9 of the 17 independent mutations found. These results suggest that up to 1 in 10 normal individuals may harbor a significant frequency of oncogenic mutations in circulating leukocytes.

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