DNA methylation as a target for drug design

被引:83
作者
Bender, CM [1 ]
Zingg, JM [1 ]
Jones, PA [1 ]
机构
[1] Univ So Calif, Sch Med, Norris Comprehens Canc Ctr, Urol Canc Res Lab, Los Angeles, CA 90033 USA
关键词
DNA methylation; 5-methylcytosine; cancer; 5-Aza-2 '-deoxycytidine;
D O I
10.1023/A:1011946030404
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
DNA methylation is essential for normal embryonic development. Distinctive genomic methylation patterns must be formed and maintained with high fidelity to ensure the inactivities of specific promoters during development. The mutagenic and epigenetic aspects of DNA methylation are especially interesting because they may lead to the inactivation of genes which are involved in human carcinogenesis. The mutagenicity of 5-Methylcytosine (5mC) and the role of promoter hypermethylation in gene silencing, particularly in cancer, suggest a clinical significance for the design of novel DNA methylation inhibitors which may be utilized to reverse the effects of DNA methylation.
引用
收藏
页码:175 / 187
页数:13
相关论文
共 155 条
[21]   CORRELATION BETWEEN HYPOMETHYLATION OF DNA AND EXPRESSION OF GLOBIN GENES IN FRIEND ERYTHROLEUKEMIA CELLS [J].
CHRISTMAN, JK ;
PRICE, P ;
PEDRINAN, L ;
ACS, G .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1977, 81 (01) :53-61
[22]   THE CPG DINUCLEOTIDE AND HUMAN GENETIC-DISEASE [J].
COOPER, DN ;
YOUSSOUFIAN, H .
HUMAN GENETICS, 1988, 78 (02) :151-155
[23]  
Costello JF, 1996, CANCER RES, V56, P2405
[24]  
COULTER AW, 1974, MOL PHARMACOL, V10, P319
[25]  
COULTER AW, 1974, MOL PHARMACOL, V10, P293
[26]  
COULTER AW, 1974, MOL PHARMACOL, V10, P305
[27]   Cell proliferation and global methylation status changes in mouse liver after phenobarbital and/or choline-devoid, methionine-deficient diet administration [J].
Counts, JL ;
Sarmiento, JI ;
Harbison, ML ;
Downing, JC ;
McClain, RM ;
Goodman, JI .
CARCINOGENESIS, 1996, 17 (06) :1251-1257
[28]  
CREUSOT F, 1982, J BIOL CHEM, V257, P2041
[29]   MOLECULAR AND CYTOLOGICAL EVIDENCE OF S-ADENOSYL-L-HOMOCYSTEINE AS AN INNOCUOUS UNDERMETHYLATING AGENT IN-VIVO [J].
DECABO, SF ;
SANTOS, J ;
FERNANDEZPIQUERAS, J .
CYTOGENETICS AND CELL GENETICS, 1995, 71 (02) :187-192
[30]   S-ADENOSYLHOMOCYSTEINE HYDROLASE INHIBITORS AS BROAD-SPECTRUM ANTIVIRAL AGENTS [J].
DECLERCQ, E .
BIOCHEMICAL PHARMACOLOGY, 1987, 36 (16) :2567-2575