This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lock, R. B. Articles by Ross, W. E. Search for Related Content PubMed Articles by Lock, R. B. Articles by Ross, W. E.

Possible Role for p34^cdc2 Kinase in Etoposide-induced Cell Death of Chinese Hamster Ovary Cells¹

The J. Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40292

In an effort to shed light upon the processes of antitumor drug-induced cell death, we have carried out a systematic study of the effects of the anti-topoisomerase II agent, etoposide, on Chinese hamster ovary cells. Treatment of Chinese hamster ovary cells for 1 h with a 2-log cell-killing concentration of etoposide induces a high incidence of DNA single-strand breaks which are rapidly repaired upon drug removal. p34^cdc2 kinase activity is inhibited within 1 h of addition of etoposide. Following removal of drug, cells accumulate transiently in G₂. Upon recovery of p34^cdc2 kinase activity (between 12 and 24 h posttreatment), approximately 50% of cells progress through mitosis which results in micronucleation. Examination of mitotic figures at various posttreatment incubation times indicates that micronucleation of daughter cells could be attributed to abnormal segregation of chromosomes during mitosis. Unexpectedly, p34^cdc2 kinase activity remains elevated relative to untreated controls until 36 h post-etoposide treatment, a point where no further cell division takes place. This activity decreases by 48 h posttreatment, concomitant with a decrease in cell viability as estimated by the ability to exclude trypan blue. These results indicate that etoposide may induce cytotoxicity via gross chromosomal fragmentation, and that p34^cdc2 kinase may be involved in this process.

¹ This work was supported by funds from the NIH (USPHS Grant CA-24586).

² To whom requests for reprints should be addressed.

³ Present address: The College of Medicine, University of Florida, Gainesville, FL 32610.

Received 10/18/89. Revised 2/14/90.

This article has been cited by other articles:

				S. Bonnaud, C. Niaudet, G. Pottier, M.-H. Gaugler, J. Millour, J. Barbet, L. Sabatier, and F. Paris Sphingosine-1-Phosphate Protects Proliferating Endothelial Cells from Ceramide-Induced Apoptosis but not from DNA Damage-Induced Mitotic Death Cancer Res., February 15, 2007; 67(4): 1803 - 1811. [Abstract] [Full Text] [PDF]

				A. J. Janss, A. Maity, C.-B. Tang, R. J. Muschel, W. G. McKenna, L. Sutton, and P. C. Phillips Decreased cyclin B1 expression contributes to G2 delay in human brain tumor cells after treatment with camptothecin Neuro-oncol, January 1, 2001; 3(1): 11 - 21. [Abstract] [PDF]

				R. J. Sleiman and B. W. Stewart Early Caspase Activation in Leukemic Cells Subject to Etoposide-induced G2-M Arrest: Evidence of Commitment to Apoptosis Rather Than Mitotic Cell Death Clin. Cancer Res., September 1, 2000; 6(9): 3756 - 3765. [Abstract] [Full Text]

				P. A. Johnson, P. Clements, K. Hudson, and K. W. Caldecott A Mitotic Spindle Requirement for DNA Damage-induced Apoptosis in Chinese Hamster Ovary Cells Cancer Res., June 1, 1999; 59(11): 2696 - 2700. [Abstract] [Full Text] [PDF]

				G. M. Kupfer, T. Yamashita, D. Naf, A. Suliman, S. Asano, and A. D. D'Andrea The Fanconi Anemia Polypeptide, FAC, Binds to the Cyclin-Dependent Kinase, cdc2 Blood, August 1, 1997; 90(3): 1047 - 1054. [Abstract] [Full Text] [PDF]

				P. R. Andreassen, F. B. Lacroix, and R. L. Margolis Chromosomes with Two Intact Axial Cores Are Induced by G2 Checkpoint Override: Evidence That DNA Decatenation Is not Required to Template the Chromosome Structure J. Cell Biol., January 13, 1997; 136(1): 29 - 43. [Abstract] [Full Text] [PDF]

				W Ongkeko, D. Ferguson, A. Harris, and C Norbury Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage J. Cell Sci., January 8, 1995; 108(8): 2897 - 2904. [Abstract] [PDF]