Altered DNA methylation: A secondary mechanism involved in carcinogenesis

被引:87
作者
Goodman, JI [1 ]
Watson, RE [1 ]
机构
[1] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA
关键词
DNA methyltransferase; imprinting; maintenance methylase; 5-methylcytosine; risk assessment;
D O I
10.1146/annurev.pharmtox.42.092001.141143
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how,, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?.
引用
收藏
页码:501 / 525
页数:25
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共 154 条
[1]  
ABANOBI SE, 1982, CANCER RES, V42, P412
[2]   INCREASED G+C CONTENT OF DNA STABILIZES METHYL CPG DINUCLEOTIDES [J].
ADAMS, RLP ;
EASON, R .
NUCLEIC ACIDS RESEARCH, 1984, 12 (14) :5869-5877
[3]   CHEMICAL CARCINOGENESIS - TOO MANY RODENT CARCINOGENS [J].
AMES, BN ;
GOLD, LS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (19) :7772-7776
[4]  
Baasner S, 1996, ONCOGENE, V13, P901
[5]   Carcinogenesis in mouse and human cells: parallels and paradoxes [J].
Balmain, A ;
Harris, CC .
CARCINOGENESIS, 2000, 21 (03) :371-377
[6]   THE MOUSE INSULIN-LIKE GROWTH-FACTOR TYPE-2 RECEPTOR IS IMPRINTED AND CLOSELY LINKED TO THE TME LOCUS [J].
BARLOW, DP ;
STOGER, R ;
HERRMANN, BG ;
SAITO, K ;
SCHWEIFER, N .
NATURE, 1991, 349 (6304) :84-87
[7]   Tying it all together: Epigenetics, genetics, cell cycle, and cancer [J].
Baylin, SB .
SCIENCE, 1997, 277 (5334) :1948-1949
[8]   Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis [J].
Belinsky, SA ;
Nikula, KJ ;
Palmisano, WA ;
Michels, R ;
Saccomanno, G ;
Gabrielson, E ;
Baylin, SB ;
Herman, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) :11891-11896
[9]   Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene [J].
Bell, AC ;
Felsenfeld, G .
NATURE, 2000, 405 (6785) :482-485
[10]   CLONING AND SEQUENCING OF A CDNA-ENCODING DNA METHYLTRANSFERASE OF MOUSE CELLS - THE CARBOXYL-TERMINAL DOMAIN OF THE MAMMALIAN ENZYMES IS RELATED TO BACTERIAL RESTRICTION METHYLTRANSFERASES [J].
BESTOR, T ;
LAUDANO, A ;
MATTALIANO, R ;
INGRAM, V .
JOURNAL OF MOLECULAR BIOLOGY, 1988, 203 (04) :971-983