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
Al. Kung et al., 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, The Journal of biological chemistry, 268(31), 1993, pp. 23072-23080
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.