Diphtheria toxin resistance in human lymphoblast lines

Stable mutants (Dipr), highly resistant to diphtheria toxin have been selected from a sensitive human lymphoblast line. A second human lymphoblast line, HH-4 (and its derivative TK6-1) were found to be highly resistant to diphtheria toxin without any previous selection, suggesting the presence of the Dipr allele in the human population. The resistance of protein synthesis in extracts of mutant cells to diphtheria toxin indicates that the genetic lesion in the resistant lines examined involved an alteration in the protein synthesis. In comparison to sensitive cells, the mutant cell extracts contained reduced (30–40%) levels of ADP-ribosylatable elongation factor-2 activity suggesting that the lesion presumably affects elongation factor-2 in such cells. The biochemical phenotype of these mutants appears similar to that of the DiprIIb class of mutants of Chinese hamster cells (4,6) which behave codominantly in hybrids.