Inhibition of cell division by interferon: changes in cell cycle characteristics and in morphology of Ehrlich ascites tumour cells in culture

Abstract

The rate of division of Ehrlich ascites tumour cells in culture is inhibited by mouse interferon. A 75% reduction in cell number is achieved after 3 days and this effect is species specific. The growth inhibition is associated with a marked increase in modal cell volume and with extensive changes in cellular morphology. The cells also become more resistant to detachment from the substratum by mild trypsin treatment. Analysis of the duration of specific phases of the cell cycle indicates prolongation of mitosis (by 150%), G2 (by 44%) and S-phase (by 100%), but a slight shortening of G1, as a result of interferon treatment. There is also a dramatic rise in the proportion of cells in culture which contain 2 or more nuclei. As a result of these changes, together with the increase in cell size, the mean cellular contents of protein, RNA and DNA are considerably elevated. There is a small but significant increase in 3′5′ cyclic AMP (cAMP) content of Ehrlich cells after exposure to interferon, and exogenous cAMP or its analogues cause morphological changes similar to those elicited by interferon. However, many of the other effects of the latter are not mimicked by the cyclic nucleotide, suggesting that cAMP is only involved in part of the complex pattern of responses of cells to interferon which result in inhibition of growth and division.