|
KMID : 0043319970200060550
|
|
Archives of Pharmacal Research
1997 Volume.20 No. 6 p.550 ~ p.554
|
|
|
Sequence Specificity for DNA Interstrand cross-linking induced by anticancer drug chlorambucil
|
|
Yoon Jung-Hoon
Lee Chong-Soon
|
|
|
Abstract
|
|
|
|
Chlorambucil is known to alkylate primarily N7 of guanine and N3 of adenine to induce DNA monofunctional adducts and interstrand cross-links (ISC). We have investigated the sequence specificity for DNA ISC induced by chlorambucil using duplex oligomers containing a defined cross-linkable sequences under bar which asterisk indicates the potential cross-linking site and underlined base indicates the potential cross-linking site on the opposite strand. An analysis of 20% denaturing polyacrylamide gel electrophoresis showed that chlorambucil was albe to induce DNA ISC in the duplex oligomers containing a sequence . The formation of DNA ISC was not observed in the duplex oligomers containing sequences . or . These results indicate that chlorambucil induces guanine-guanine DNA ISC but not guanine-adenine or adenine-adenine DNA ISC. In addition, we have tested the ability of chlorambucil to induce DNA ISC within or sequences using duplex oligomers containing the sequence. The result of DNA strand cleavage assay showed that DNA ISC was formed at the sequence (an 1,3 cross-link, ) but not at (an 1,4 cross-link, ) or sequence (an 1,2 cross-link, ).
|
|
|
KEYWORD
|
|
|
Anticancer drug, Sequence specificity, Chlorambucil, DNA interstrand cross-links
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|