Effect of cytolethal distending toxin on F-actin assembly and cell division in Chinese hamster ovary cells.
Cytolethal distending toxin (CDT) is a newly described toxin produced by a number of enteropathogens, including Campylobacter jejuni, various Escherichia coli strains, and a few Shigella species. CDT induces distension and eventual death of a number of transformed cell lines. Here, we extend previous studies by demonstrating that morphological changes in CDT-treated Chinese hamster ovary cells are coincident with changes in cytoskeletal structure and an inhibition of cell proliferation. CDT-treated cells underwent a progressive accumulation of F-actin assemblies which microscopically resembled actin stress fibers. Accumulation of the stress fiber-like structures in CDT-treated cells was accompanied by an apparent blockage of cell division. Multinucleation was detected in some cells but did not constitute a significant feature of CDT action. Although toxin-treated cells failed to divide, cell viability remained high for the first 4 days following toxin treatment, as evidenced by trypan blue exclusion and neutral red uptake. [3H]thymidine incorporation studies on CDT-treated cells were consistent with a blockage of cell proliferation without a direct inhibition of DNA synthesis. Although the progression of toxin action developed slowly, a 2-min exposure to CDT resulted in an irreversible development of toxicity. Together, our data indicate that CDT affects F-actin assembly within target cells and may interrupt the regulation or function of cell cycle-dependent events leading to cytokinesis.
Aragon
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V
Division of Cell Biology and Biophysics, University of Missouri-Kansas City, 64110, USA.
Chao
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K
Dreyfus
L A
LA
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis; D008855:Microscopy, Electron, Scanning
D000199:Actins; D001427:Bacterial Toxins; C067044:cytolethal distending toxin; D004247:DNA