Siegfried J M, Tritton T R, Sartorelli A C
Eur J Cancer Clin Oncol. 1983 Aug;19(8):1133-41. doi: 10.1016/0277-5379(83)90039-1.
Sublines of sarcoma 180 (S180) of varying sensitivity to adriamycin (ADR) have been selected in culture. The degree of resistance of these sublines ranged from 6- to 125-fold above that of parent S180 cells. ADR-resistant sublines demonstrated comparable degrees of cross-resistance to daunomycin (DNR), marcellomycin and AD 32, but each subline showed a uniform degree of tolerance toward actinomycin D and vincristine. Compared to the anthracycline-sensitive parent tumor, a 40% decrease in the intracellular steady-state level of [3H]-daunomycin was observed in all sublines regardless of the degree of resistance. The level of cell-associated DNR and ADR observed after administration of equipotent concentrations of drug was different for each cell line and increased in proportion to the drug concentration. Thus, altered drug permeability appeared to be of minimal importance in the expression of high levels of resistance. In addition, the extent of DNR metabolism by the anthracycline-resistant sublines was not sufficiently different from that seen in parent S180 cells to account for the observed tolerance to these agents.
已在培养中筛选出对阿霉素（ADR）敏感性不同的肉瘤180（S180）亚系。这些亚系的耐药程度比亲代S180细胞高6至125倍。阿霉素耐药亚系对柔红霉素（DNR）、马塞洛霉素和AD 32表现出相当程度的交叉耐药，但每个亚系对放线菌素D和长春新碱表现出一致的耐受程度。与对蒽环类药物敏感的亲代肿瘤相比，所有亚系中无论耐药程度如何，[3H] - 柔红霉素的细胞内稳态水平均下降40%。给予等效浓度药物后观察到的细胞相关DNR和ADR水平因每个细胞系而异，并与药物浓度成比例增加。因此，药物通透性改变在高水平耐药表达中似乎不太重要。此外，蒽环类耐药亚系对DNR的代谢程度与亲代S180细胞中所见的差异不足以解释观察到的对这些药物的耐受性。
