TY - JOUR
T1 - Alterations in the X chromosome replication pattern induced by 5-azacytidine in a human tumor line
AU - Gregory, Paula
AU - Wang, Nancy
N1 - Funding Information:
This work was supported by the Hayward Foundation.
PY - 1986/2/15
Y1 - 1986/2/15
N2 - Biochemical studies have shown that the cytosine analog, 5-azacytidine (5-azaC), induces hypomethylation and reactivates specific X-linked genes. Cytogenetically, it has been shown that this hypomethylating agent alters the replication pattern of the late-replicating, inactive X chromosome. In order to analyze the effect of 5-azaC on the X chromosome replication pattern of tumor cells with multiple X chromosomes, 5-azaC treatment, followed by terminal bromodeoxyuridine (BrdU) pulses, was applied to the human breast tumor cell line ZR-75-30. Metaphase spreads were analyzed for the presence of X chromosomes with altered replication banding patterns. Seventy-four percent of the untreated cells contained at least one typical, pale-staining, inactive X chromosome as compared to only 8% of the cells in the treated groups. This demonstrates a dramatic change in the replication pattern of the inactive X chromosome of these neoplastic cells in response to 5-azaC treatment. These results suggest that neoplastic tissue is highly responsive to this hypomethylating agent, which may be related to the high degree of DNA hypomethylation observed in neoplasias.
AB - Biochemical studies have shown that the cytosine analog, 5-azacytidine (5-azaC), induces hypomethylation and reactivates specific X-linked genes. Cytogenetically, it has been shown that this hypomethylating agent alters the replication pattern of the late-replicating, inactive X chromosome. In order to analyze the effect of 5-azaC on the X chromosome replication pattern of tumor cells with multiple X chromosomes, 5-azaC treatment, followed by terminal bromodeoxyuridine (BrdU) pulses, was applied to the human breast tumor cell line ZR-75-30. Metaphase spreads were analyzed for the presence of X chromosomes with altered replication banding patterns. Seventy-four percent of the untreated cells contained at least one typical, pale-staining, inactive X chromosome as compared to only 8% of the cells in the treated groups. This demonstrates a dramatic change in the replication pattern of the inactive X chromosome of these neoplastic cells in response to 5-azaC treatment. These results suggest that neoplastic tissue is highly responsive to this hypomethylating agent, which may be related to the high degree of DNA hypomethylation observed in neoplasias.
UR - http://www.scopus.com/inward/record.url?scp=0022613502&partnerID=8YFLogxK
U2 - 10.1016/0165-4608(86)90082-8
DO - 10.1016/0165-4608(86)90082-8
M3 - Article
C2 - 2417699
AN - SCOPUS:0022613502
SN - 0165-4608
VL - 20
SP - 263
EP - 267
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
IS - 3-4
ER -