Rouscilles A, Houee-Levin C, Gardes-Albert M, Ferradini C
Laboratoire de Chimie Physique, Université René Descartes, Paris, France.
Free Radic Biol Med. 1989;6(1):37-43. doi: 10.1016/0891-5849(89)90157-3.
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.
利用γ辐射分解产生的COO-自由基作为还原剂,研究了嵌入DNA中的柔红霉素的还原过程。发现嵌入DNA中的药物还原过程与无DNA的水溶液中柔红霉素的还原过程非常相似。(a)最终产物相同(7-脱氧柔红霉酮);(b)还原产率相同[(2.6±0.2)×10-7 mol·J-1];(c)H2O2与对苯二酚柔红霉素反应,一步反应使药物再生。然而,7-脱氧柔红霉酮的沉淀非常缓慢,以至于这种糖苷配基可被COO-自由基还原为其对苯二酚形式,而在无DNA的情况下无法观察到这种形式。这表明整个4电子还原过程在DNA中发生。讨论了这些发现的意义。