Alterations in the X chromosome replication pattern induced by 5-azacytidine in a human tumor line.
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.
Gregory
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P
Wang
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N
D001374:Azacitidine / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002460:Cell Line; D002871:Chromosome Banding; D004261:DNA Replication / Q000187:drug effects*; D004303:Dosage Compensation, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008745:Methylation; D014960:X Chromosome
D001374:Azacitidine