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The Journal of Cell Biology, Vol 61, 481-500, Copyright © 1974 by Rockefeller University Press

ARTICLE

ACTION OF CYTOCHALASIN D ON CELLS OF ESTABLISHED LINES

: I. Early Events



Armand F. Miranda 1, Gabriel C. Godman 1, Arline D. Deitch 1, and Stuart W. Tanenbaum 1

1 From the Departments of Pathology and Microbiology, Columbia University, New York 10032.

Dr. Tanenbaum's present address is School of Biology, Chemistry, and Ecology, State University of New York College of Environmental Science, Syracuse, New York 13210.

HeLa, Vero, L, HEp2, and MDBK cells respond immediately to 0.2–0.5 µg/ml cytochalasin D (CD) with sustained contraction (contracture), loss of microvilli, expression of endoplasmic contents (zeiosis), nuclear protrusion, and extension of cytoplasmic processes. The development of these changes is depicted, and the dose-response patterns in these cell lines are described. MDBK is generally most resistant and HeLa most sensitive to these effects of CD. Cells in G1 are most sensitive to CD; responsiveness decreases progressively during early S and is least in mid S through G2. CD inhibits transport of [14C]deoxyglucose in HeLa by about 45% but has no significant effect on hexose uptake in Vero and MDBK; sugar transport is thus apparently unrelated to any morphologic effect of CD. Although spreading and attachment are impeded, CD does not decrease and may even enhance the adhesiveness of established monolayers. Contraction appears to be a primary early effect of CD, upon which other visible changes follow. It is prevented by some inhibitors of energy metabolism (deoxyglucose and dinitrophenol) and does not occur in glycerinated models without ATP. The possible bases of the contractile response to CD are discussed. Although direct or indirect action of CD on some microfilaments may occur, a generalized structural disruption of contractile filaments by CD is considered unlikely.

Submitted on July 26, 1973
Revised on January 27, 1974


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