GENOMIC METHYLATION--A MECHANISM TO ALTER PHENOTYPES

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DESCRIPTION: The long-term goal is to determine how changes in the genomic pattern of 5-methylcytosine regulates expression of drug resistance genes in human tumor cells. Human multiple myeloma cell lines and drug resistant variants which have either lost the activity of a DNA repair protein, MGMT (06-methylguanine DNA methyltransferase), or overexpress the multidrug resistance gene (MDRl) will be used. The specific aims include studies (1) on clinical specimens to determine if patients that received verapamil treatment are sensitized to nitrosoureas, (2) to determine the cellular mechanisms that control MGMT and MDRl gene expression, and (3) to identify new DNA sequences that may be important in drug resistance.