Alteration in morphology of Chinese hamster ovary cells by Ni 3S 2 and dibutyryl cAMP

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Rounded Chinese hamster ovary cells (CHO) (axial ratio, 1:1) elongated (axial ratio, >;1:3) when exposed to Ni 3S 2. Other metal compounds which were tested had only minor effects on CHO morphology over a wide range of concentrations. These cells were elongated following exposure to Ni 3S 2 at concentrations which did not affect cell proliferation as judged by cell doubling and colony formation. The elongation occurred when agents that elevate intracellular cAMP concentrations were added to cultures. The cells treated with either dibutyryl cAMP or Ni 3S 2 had very similar fibroblastic morphology. Upon removal of media containing dibutyryl cAMP, elongated CHO cells reverted to control morphology within 4 hr. In contrast, the cultures previously treated with Ni 3S 2 did not rapidly revert to normal morphology. Nickel subsulfide activated cAMP-dependent protein kinase within 3 hr after its addition to cultures while NiS or NiCl 2 did not significantly activate protein kinase. Dibutyryl cAMP addition to CHO cultures completely activated this enzyme. High doses of actinomycin D, or cycloheximide did not affect the dibutyryl cAMP-induced elongation of CHO cells while addition of colcemid did. All three of these agents inhibited the Ni 3S 2 elongation of CHO cells. These data demonstrate that Ni 3S 2 induced morphological changes in CHO cells are similar to the morphological changes mediated by cAMP.