TY - JOUR
T1 - Suppression of tumorigenicity mediated by 5-azacytidine and associated with increased chromosome number
AU - Walker, C.
AU - Matthews, A. M.
AU - Shay, J. W.
N1 - Funding Information:
I Received March 14, 1986; revised September 10, 1986; accepted September 29, 1986. 2 Supported in part by grant DCB8317788 from the National Science Foundation and by Public Health Service grant CA-40065 from the Division of Extramural Activities, National Cancer Institute, to 1- W. S. 3 Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, P.O. Box 12233, Research Triangle Park, NC 27709. 4 Department of Cell Biology, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, TX 75235. 5 Address reprint requests to Dr. Shay. 6 We thank Dr. Steven Belinsky for help with high-performance liquid chromatography determinations, Mr. Andrew M. Gwie for technical assistance, and Ms. Alma Gonzalez for preparation of this manuscript.
PY - 1987/4
Y1 - 1987/4
N2 - 5-Azacytidine (5-azaC), a hypomethylating agent, was examined for the effect on a highly tumorigenic murine cell line, T984-15. While 20 of 20 untreated subclones of T984-15 produced tumors when injected into BALB/c nude mice, 14 of 15 T984-15 subclones that were treated for 24 hours with 5 μg 5-azaC/ml displayed suppressed tumorigenesis under identical conditions. Of the 14 clones that were suppressed, 12 were nontumorigenic and 2 showed a greatly increased latency. Chromosome analyses of 5-azaC-treated nontumorigenic clones revealed that, in contrast to untreated tumorigenic controls (median chromosome number 49-59), 9 of 10 5-azaC-treated nontumorigenic clones analyzed displayed an elevated chromosome complement (68–94 chromosomes/cell). The increase in chromosome number occurred progressively with time, following a single 24-hour 5-azaC treatment, indicating that 5-azaC was not selecting for a subpopulation of cells with an elevated chromosome complement. The evidence that the hypomethylating agent 5-azaC can suppress a cell’s tumorigenic potential and that this suppression correlates with increased chromosome number suggests that 5-azaC modulates cellular phenotypes by mechanisms that involve alterations in a cell’s chromosome complement.
AB - 5-Azacytidine (5-azaC), a hypomethylating agent, was examined for the effect on a highly tumorigenic murine cell line, T984-15. While 20 of 20 untreated subclones of T984-15 produced tumors when injected into BALB/c nude mice, 14 of 15 T984-15 subclones that were treated for 24 hours with 5 μg 5-azaC/ml displayed suppressed tumorigenesis under identical conditions. Of the 14 clones that were suppressed, 12 were nontumorigenic and 2 showed a greatly increased latency. Chromosome analyses of 5-azaC-treated nontumorigenic clones revealed that, in contrast to untreated tumorigenic controls (median chromosome number 49-59), 9 of 10 5-azaC-treated nontumorigenic clones analyzed displayed an elevated chromosome complement (68–94 chromosomes/cell). The increase in chromosome number occurred progressively with time, following a single 24-hour 5-azaC treatment, indicating that 5-azaC was not selecting for a subpopulation of cells with an elevated chromosome complement. The evidence that the hypomethylating agent 5-azaC can suppress a cell’s tumorigenic potential and that this suppression correlates with increased chromosome number suggests that 5-azaC modulates cellular phenotypes by mechanisms that involve alterations in a cell’s chromosome complement.
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U2 - 10.1093/jnci/78.4.695
DO - 10.1093/jnci/78.4.695
M3 - Article
C2 - 2435944
AN - SCOPUS:0023258737
SN - 0027-8874
VL - 78
SP - 695
EP - 700
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 4
ER -