DIFFERENCES IN THE REGULATION OF PROTEIN-SYNTHESIS, CYCLIN-B ACCUMULATION, AND CELLULAR GROWTH IN RESPONSE TO THE INHIBITION OF DNA-SYNTHESIS IN CHINESE-HAMSTER OVARY AND HELA S3 CELLS

We have shown previously that there are significant differences betwee n mammalian cell lines in response to disruption of the assembly of th e mitotic spindle apparatus (Kung, A. L., Sherwood, S. W., and Schimke , R. T. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 9553-9557). In this paper we report that there are also significant differences between m ammalian cell lines in response to the inhibition of DNA synthesis. In HeLa S3 cells protein synthesis is down-regulated, and cellular growt h is arrested in response to the inhibition of DNA synthesis. Upon rel ease from inhibition and resumption of normal growth, cellular viabili ty is maintained near untreated control levels. In contrast, Chinese h amster ovary cells continue to accumulate protein and continue to unde rgo cellular growth during the period of DNA synthesis inhibition. Cyc lin B levels accumulate throughout the period of inhibition and rapidl y exceed normal levels at mitosis. The degree of aberrant growth durin g the period of transient DNA synthesis inhibition is directly related to the degree of subsequent cytotoxicity. If protein accumulation and cellular growth are limited with partially inhibitory levels of cyclo heximide during the period of DNA synthesis inhibition, the cytotoxic effects are abolished. These results support the concept that aberrant growth and accumulation of proteins during a transient period of DNA synthesis inhibition are primary determinants of subsequent cell killi ng.