GENOMIC METHYLATION--A MECHANISM TO ALTER PHENOTYPES

描述：长期目标是确定 5-甲基胞嘧啶的基因组模式调控药物的表达 人类肿瘤细胞中的耐药基因。人多发性骨髓瘤细胞 已经失去活性的品系和抗药性变异体 DNA修复蛋白MGMT(06-甲基鸟嘌呤DNA甲基转移酶)， 或过表达多药耐药基因(MDR1)将被使用。这个 具体目标包括研究(1)临床标本，以确定 接受维拉帕米治疗的患者对 亚硝脲，(2)确定控制MGMT的细胞机制 和mdr1基因的表达，以及(3)鉴定可能 在抗药性方面发挥重要作用。

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.