这项研究评估了两种蒽环类抗生素多柔比星和伊达比星（4-去甲氧雪莲素）的主要代谢产物对小鼠成纤维肉瘤935.1细胞的DNA损伤能力。由于蒽环类抗生素引起的DNA损伤可能是通过拓扑异构酶II介导的，因此我们也表征了这些药物抑制该酶的能力。将多柔比星和伊达比星的C-13醇和无糖基代谢物与母药进行比较，根据滤纸析测量的单链DNA断裂判断其诱导DNA单链断裂的效力。在整个细胞中，C-13醇代谢物所产生的最大DNA链断裂与其各自的母药相似。然而，在孤立的细胞核中，这些醇代谢物的效力比母药高出两倍。无糖基代谢物对整个细胞和细胞核的损伤都很少。多柔比星化合物与伊达比星化合物在诱导DNA损伤的能力和细胞毒性之间存在显著差异。多柔比星和多柔比星醇的细胞毒性作用（0.2和4微米时达到50%的细胞生长抑制）与细胞DNA断裂的明显诱导（在药物浓度方面）相一致。相反，为了达到50%的生长抑制，伊达比星和伊达比星醇所需的浓度（分别为0.005和0.006微米）约比诱导DNA损伤的药物水平低20倍。这六种化合物都抑制了分离的拓扑异构酶II的催化活性。虽然C-13醇代谢物在浓度为5-10微米时也产生了这种抑制作用，但无糖基代谢物的活性仍然远远不及这些药物。（250字后的摘要被截断。）

This study assessed the ability of major metabolites of two types of anthracycline antibiotics, doxorubicin and idarubicin (4-demethoxydaunorubicin) to damage DNA in mouse fibrosarcoma 935.1 cells. Since DNA lesions by anthracyclines may be mediated by topoisomerase II, we also characterized the ability of the drugs to inhibit this enzyme. The C-13 alcohol and aglycone metabolites of doxorubicin and idarubicin were compared to the parent drugs in terms of induction of DNA single strand breaks measured by filter elution. In whole cells, the maximal DNA strand breakage induced by the C-13 alcohol metabolites was similar to that of their respective parent drugs. In isolated nuclei, however, the alcohol metabolites were two times more potent than the parent drugs. The aglycone metabolites produced very little damage in either whole cells or nuclei. The doxorubicin compounds differed markedly from idarubicin drugs in the way their ability to induce DNA breaks was related to cytotoxic activity. Doxorubicin and doxorubicinol cytotoxic effects (50% cell growth inhibition at 0.2 and 4 microM, respectively) coincided (in terms of drug concentrations) with the induction of significant breakage of cellular DNA. In contrast, the concentrations of idarubicin and idarubicinol needed to produce 50% growth inhibition (0.005 and 0.006 microM, respectively) were about 20 times lower than drug levels that induced significant DNA damage. All six compounds inhibited the catalytic activity of isolated topoisomerase II. While the alcohol metabolites produced this inhibition at concentrations similar to those of their parent drugs (5-10 microM), the aglycones were again much less active.(ABSTRACT TRUNCATED AT 250 WORDS)