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, [H-3]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.