Changes in morphology and cell cycle traverse induced in CHO cells by methyl isobutyl xanthine

Abstract

Methyl isobutyl xanthine (MIX) added to the medium of CHO cells induced a transient elevation of intracellular cAMP concentration. Values which were maximal after 30 min incubation in MIX subsequently declined until after 4–5 h incubation cAMP levels in MIX-treated cells were the same as those of controls. Following addition of MIX to the medium, several perturbations of cell cycle traverse were observed, including a block early in G1 which delayed progress of the cell through subsequent phases of the cell cycle by approx. 1 h, inhibition of transport of exogenous thymidine, arrest of cells in G2 and early M and more rapid completion of mitosis when MIX was added to metaphase cells. None of these changes persisted during prolonged incubation in MIX and cell cycle parameters of cells growing continuously in 0.2 mM MIX were identical with those of their control counterparts. In contrast, conversion from epithelial to fibroblast morphology induced by MIX persisted as long as MIX was maintained in the medium and thus appeared to be independent of elevation of cAMP levels. Morphological conversion was not related to any of the modifications of cell cycle traverse induced by short exposure to MIX.