title: Entry of diphtheria toxin into cells: possible existence of cellular factor(s) for entry of diphtheria toxin into cells was studied in somatic cell hybrids and hybrid toxins.
abstract: Ehrlich ascites tumor cells were found to be very insensitive to diphtheria toxin. We formed 37 hybrids from Ehrlich tumor cells and diphtheria toxin-sensitive human fibroblasts. The effects of diphtheria toxin on protein synthesis in those hybrids were examined. The hybrids were divided into three groups on the basis of toxin sensitivity. Group A hybrids were as sensitive to diphtheria toxin as human fibroblasts, Group C were as resistant as Ehrlich tumor cells, and Group B had intermediate sensitivity. Group A hybrids had diphtheria toxin-binding sites but Group B and C had no detectable binding sites. Elongation factor-2 of all the hybrids was susceptible to ADP-ribosylation by fragment A of diphtheria toxin. Cells of Group A and B became more sensitive to CRM 45 (cross-reacting material 45 of diphtheria toxin) after they were exposed to low pH (pH = 4.5). The resistance of Group C to CRM 45 was not affected by the same treatment. Group A and B hybrids and human fibroblasts had similar sensitivities to a hybrid toxin composed of wheat germ agglutinin and fragment A of diphtheria toxin, but Group C and Ehrlich tumor cells were resistant to this hybrid toxin. All the hybrids and Ehrlich tumor cells were more sensitive to a hybrid toxin composed of wheat germ agglutinin and subunit A of ricin than were human fibroblasts. On subcloning of Group B hybrids, one Group C hybrid was obtained, but no Group A hybrid. These facts suggest that Ehrlich ascites tumor cells differ from human fibroblasts in the expression of a factor(s) that is involved in entry of fragment A of diphtheria toxin into the cytoplasm after the toxin binds to its surface receptors.
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004167:Diphtheria Toxin / Q000378:metabolism* / Q000633:toxicity; D005347:Fibroblasts / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D051379:Mice; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
chemical_list: D004167:Diphtheria Toxin; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D000246:Adenosine Diphosphate Ribose