Takeshita H, Kusuzaki K, Murata H, Nakamura S, Ashihara T, Hirasawa Y
Department of Orthopaedic Surgery, Kyoto Prefectural University of Medicine, Japan.
Anticancer Res. 1999 Nov-Dec;19(6B):5235-8.
To study the influence of cellular DNA content on the accumulation and efficacy of doxorubicin (DOX), we characterized P-glycoprotein (Pgp)-positive and -negative murine osteosarcoma cell clones that had a different DNA index. Statistical analysis demonstrated that the cytotoxic effects of DOX correlated significantly with the ratio of intracellular DOX accumulation divided by the cellular DNA content (DOX/DNA ratio) (P = 0.001), but not with the intracellular DOX accumulation (P = 0.16). We also tested this relationship for Pgp-negative human osteosarcoma cell lines with a different DNA ploidy, and found that these Pgp-negative cell lines all had similar DOX/DNA ratios. These results indicate that the DOX/DNA ratio is a determinant for the effects of DOX in osteosarcoma cells, regardless of their Pgp status and DNA ploidy. Thus, consideration of the cellular DNA content as well as the intracellular DOX accumulation is important to accurately detect DOX resistance.
为研究细胞DNA含量对阿霉素（DOX）蓄积及疗效的影响，我们对具有不同DNA指数的P - 糖蛋白（Pgp）阳性和阴性小鼠骨肉瘤细胞克隆进行了表征。统计分析表明，DOX的细胞毒性作用与细胞内DOX蓄积量除以细胞DNA含量的比值（DOX/DNA比值）显著相关（P = 0.001），但与细胞内DOX蓄积量无关（P = 0.16）。我们还对具有不同DNA倍性的Pgp阴性人骨肉瘤细胞系测试了这种关系，发现这些Pgp阴性细胞系均具有相似的DOX/DNA比值。这些结果表明，无论骨肉瘤细胞的Pgp状态和DNA倍性如何，DOX/DNA比值都是DOX对其作用的一个决定因素。因此，考虑细胞DNA含量以及细胞内DOX蓄积量对于准确检测DOX耐药性很重要。
