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An approach to a selection system for adenosine-deaminase-positive (ADA+) cells and detection of rat ADA+ “revertants”

✍ Scribed by Rochelle Hischhorn; Amy Ellenbogen; Frank Martiniuk


Publisher
John Wiley and Sons
Year
1985
Tongue
English
Weight
754 KB
Volume
123
Category
Article
ISSN
0021-9541

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✦ Synopsis


We have substituted deoxyadenosine or adenosine for hypoxanthine in t h e standard HAT selection system in an attempt to select for ADA-normal (ADA+) cells. ADA-human lymphoid line cells could not utilize deoxyadenosine as an alternative to hypoxanthine as a purine source (DAT) and failed to grow but were only somewhat inhibited in growth when adenosine was substituted for hypoxanthine (AAT). In contrast, ADA+ cells utilized adenosine or deoxyadenosine as efficiently as hypoxanthine as a purine source. Growth in DAT, but not in HAT, of an artificial mixture of one ADA+ human lymphoid cells in 1,000 ADA-cells resulted in enrichment of ADA+ cells to 25-86% of total cells. When we grew a rat ADA-cell line in two variations of the DAT system, we detected at least three electrophoretically different ADA+ patterns, one of which corresponded to normal rat ADA. These could represent "revertants." Genetic deficiency of the enzyme adenosine deaminase (ADA) gives rise to a fatal infantile syndrome of severe combined immunodeficiency (SCID) . Transplantation with bone marrow from a histocompatible, related donor leads