Diphtheria toxin sensitivity in a monochromosomal hybrid containing human chromosome 5.
Among the mouse-human hybrids prepared in our laboratory one clone was found to contain only human chromosome 5 with an integrated selectable marker. This monochromosomal hybrid was used to investigate different aspects related to the toxicity of diphtheria toxin (DT). The hybrid was as sensitive to diphtheria toxin as the human donor cells. The protective effect of NH4Cl against diphtheria toxin could be demonstrated in the hybrid and also in the mouse and human cell lines. The reversal of the protective NH4Cl effect at acid pH also could be demonstrated in all three cell types. Incubation of cells with 125I-diphtheria toxin at 37 degrees C in the presence of methylamine showed a time-dependent increase in specific association in the human and the hybrid but not in the mouse cell line. The results obtained for the first time on a stable monochromosomal hybrid suggest that chromosome 5 is both necessary and sufficient for the expression of DT sensitivity.
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002905:Chromosomes, Human, 4-5; D004167:Diphtheria Toxin / Q000378:metabolism / Q000633:toxicity*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins; D007621:Karyotyping; D051379:Mice; D010446:Peptide Fragments / Q000633:toxicity; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic / Q000378:metabolism
D004167:Diphtheria Toxin; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; C029795:diphtheria toxin fragment A; D000643:Ammonium Chloride