DNA-binding characteristics of aclarubicin as compared with daunorubicin and doxorubicin.
The effect of ionic strength on aclarubicin - DNA complexes was studied in comparison with its effect on daunorubicin - or doxorubicin - DNA complexes, using the spectrophotometric method. The hypochromic shift of aclarubicin, induced by its binding to native DNA, decreased to a lesser extent by the addition of Na+ than those of daunorubicin and doxorubicin, which suggests that aclarubicin-native DNA complexes are the most stable at high ionic strength. Similar examinations were made with heat-denatured DNA and polyvinyl sulfate (PVS). Aclarubicin-denatured DNA complexes showed a greater decrease in the hypochromic shift by the addition of Na+ than the corresponding complexes with native DNA. However, for daunorubicin and doxorubicin, there were no significant differences between the complexes of anthracyclines with native and denatured DNAs. In addition, the hypochromic shift of aclarubicin-PVS complexes decreased more prominently by the addition of Na+ than those of daunorubicin - and doxorubicin - PVS complexes. These results suggest that the electrostatic interaction of aclarubicin with DNA is more labile than that of daunorubicin and doxorubicin, since anthracyclines bind to single-stranded DNA and polyelectrolytes primarily by electrostatic interaction. Therefore, the other types of interaction, which may be stronger than that of daunorubicin and doxorubicin, seem to be associated with the higher stability of aclarubicin-native DNA complexes at high ionic strength. The structural differences between aclarubicin and daunorubicin or doxorubicin are considered to contribute to the differences in DNA-binding characteristics observed in this study.
Ando
S
S
First Department of Medicine, Fukui Medical School, Japan.
Kamiya
K
K
Yoshimura
T
T
Tsutani
H
H
Ueda
T
T
Uchida
M
M
Nakamura
T
T
Uchino
H
H
D015250:Aclarubicin; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D003630:Daunorubicin / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism*; D009279:Naphthacenes / Q000378:metabolism; D009994:Osmolar Concentration; D011145:Polyvinyls / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology
D009279:Naphthacenes; D011145:Polyvinyls; C019050:polyvinyl sulfate; D015250:Aclarubicin; D004317:Doxorubicin; D004247:DNA; D012964:Sodium; D003630:Daunorubicin