Killing of cultured hepatocytes by conjugates of asialofetuin and EGF linked to the A chains of ricin or diphtheria toxin.
A disulfide-linked conjugate between asialofetuin (ASF) and the toxic A chain (RTA) of ricin is as potent a toxin for cultured rat hepatocytes as our previously described conjugate between ASF and fragment A of diphtheria toxin (DTA). An RTA conjugate of epidermal growth factor (EGF) was a potent toxin for 3T3 cells. In contrast, EGF-DTA was essentially nontoxic for 3T3 cells. We have now examined the toxicity of EGF-RTA and EGF-DTA on cultured hepatocytes. The EGF-DTA conjugate, nontoxic to 3T3 cells, is also a potent toxin for hepatocytes. We also observed a decrease with time of culture in the sensitivity of hepatocytes to the ASF and EGF conjugates. This decrease is not a result of a decrease in EGF or asialoglycoprotein receptors.
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004167:Diphtheria Toxin / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors; D060748:Fetuins; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D014176:Protein Biosynthesis; D055503:Protein Multimerization; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D012276:Ricin / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000494:pharmacology*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D004167:Diphtheria Toxin; D060748:Fetuins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D000509:alpha-Fetoproteins; C017029:asialofetuin; C029795:diphtheria toxin fragment A; D004815:Epidermal Growth Factor; D012276:Ricin; D066246:ErbB Receptors