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Induction of HLA mutations by chemical mutagens in human lymphoid cells

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Abstract

We studied the effects of mutagens on the frequency of HLA “loss” variants in the diploid human lymphoid cell line T5-1, as well as the stability of mutagen-induced variants and the extent of the genetic lesions induced. Mutagens used were of different types, and included ethyl methanesulfonate (EMS), ICR-191 (ICR), and mitomycin C. Variant frequency was determined seven days after a 24-hour exposure to mutagen, by which time the cloning efficiency of exposed cultures, which was reduced following mutagenesis, had returned to normal. ICR and EMS induced dose-related increases in variant frequency of greater than two orders of magnitude at the highest concentrations tested. Mitomycin C increased variant frequency by tenfold at the one concentration tested. Seventeen of 18 induced variants showed persistence of the variant phenotype during prolonged culture following isolation. Genetic lesions induced by ICR and EMS did not extend as far as the distance between theHLA-A and -B loci (0.8 map units) in any of 21 clones tested. These data suggest a mutational origin for most mutagen-induced HLA variants of diploid cells (except for some induced by mitomycin C). Mutagenesis and mutational analysis are promising probes for studies of theHLA region.

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Abbreviations

MHC:

major histocompatibility complex

EMS:

ethyl methanesulfonate

ICR:

ICR-191

C′:

complement

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Authors and Affiliations

  1. Departments of Pediatrics and Genetics, University of Washington, 98195, Seattle, Washington

    Donald Pious, Carl Soderland & Paul Gladstone

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  1. Donald Pious
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  2. Carl Soderland
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  3. Paul Gladstone
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Pious, D., Soderland, C. & Gladstone, P. Induction of HLA mutations by chemical mutagens in human lymphoid cells. Immunogenetics 4, 437–448 (1977). https://doi.org/10.1007/BF01575679

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  • DOI: https://doi.org/10.1007/BF01575679

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