gamma-radiolysis study of the reduction by COO- free radicals of daunorubicin intercalated in DNA.
The reduction of daunorubicin intercalated in DNA was studied using COO- free radicals produced by gamma-radiolysis as reductants. The reduction process of the drug intercalated in DNA was found to be very similar to the one of daunorubicin in aqueous solution without DNA. (a) the final product is the same (7-deoxy daunomycinone); (b) the reduction yield is the same [2.6 +/- 0.2) x 10(-7) mol.J-1); (c) H2O2 reacts with hydroquinone daunorubicin giving back the drug in a one-step reaction. However 7-deoxy daunomycinone precipitation was so slow that this aglycone could be reduced by COO- free radicals giving its hydroquinone form, which cannot be observed without DNA. This shows that the whole 4-electron reduction process takes place in DNA. The implications of these findings are discussed.
Rouscilles
A
A
Laboratoire de Chimie Physique, Université René Descartes, Paris, France.
Houee-Levin
C
C
Gardes-Albert
M
M
Ferradini
C
C
D002245:Carbon Dioxide / Q000378:metabolism*; D011232:Chemical Precipitation; D004247:DNA / Q000378:metabolism*; D003630:Daunorubicin / Q000378:metabolism*; D005609:Free Radicals; D005720:Gamma Rays; D006861:Hydrogen Peroxide / Q000378:metabolism; D006873:Hydroquinones; D007364:Intercalating Agents; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D012996:Solutions; D013053:Spectrophotometry
D005609:Free Radicals; D006873:Hydroquinones; D007364:Intercalating Agents; D012996:Solutions; D002245:Carbon Dioxide; C041069:carboxyl radical; D004247:DNA; D006861:Hydrogen Peroxide; D010100:Oxygen; D003630:Daunorubicin