Alterations in the X chromosome replication pattern induced by 5-azacytidine in a human tumor line

Paula Gregory, Nancy Wang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)263-267
Number of pages5
JournalCancer Genetics and Cytogenetics
Volume20
Issue number3-4
DOIs
StatePublished - 15 Feb 1986

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