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Entry of Protein Toxins in Polarized Epithelial Cells¹

Institute for Cancer Research, the Norwegian Radium Hospital, Montebello, 0310 Oslo 3, Norway

The action of a number of toxins used in the formation of immunotoxins was studied in polarized cells. Diphtheria toxin inhibited protein synthesis most efficiently when added to the basolateral side of the kidney cells, MDCK-I, MDBK and Pt K2, and the colon carcinoma cell Caco-2. Similar findings were made with Pseudomonas aeruginosa exotoxin A in MDCK-I, Pt K2, and Caco-2 cells, and with modeccin and volkensin in MDCK-I cells. In accordance with the toxicity data, diphtheria toxin bound specifically to the basolateral side of MDCK-I cells but not to the apical side. On the other hand, in the trophoblastic BeWo cell line there was little or no difference in the toxic effect of P. aeruginosa exotoxin A and modeccin added to the two sides.

The plant toxins ricin and abrin and the bacterial Shigella toxin inhibited protein synthesis approximately equally well in all cell lines tested whether they were added apically or basolaterally. The results indicate that protein toxins are able to enter cells from both the apical and basolateral sides provided receptors are present. The consequences for the preparation of immunotoxins are discussed.

¹ Supported by the Norwegian Cancer Society, Otto and Rachel Bruuns legat, Torsteds legat, Blix legat, and the Norwegian Council for Science and the Humanities.

² Fellow of the Norwegian Cancer Society. To whom requests for reprints should be addressed.

Received 12/18/92. Accepted 2/ 5/93.

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