Ruben Z, Anderson S N, Rorig K J, Hribar J D, Bible R H
Proc Soc Exp Biol Med. 1985 Oct;180(1):84-91. doi: 10.3181/00379727-180-42147.
Cellular uptake of disobutamide (D), and clear cytoplasmic vacuoles (CCV) induction by D in cultured rat urinary bladder carcinoma cells were dependent on the culture medium pH. At pH 6.0-6.7, drug uptake was slow and no CCV formed in 24 hr. At pH 7.0-8.0, the rate of D uptake and early appearance of CCV were directly proportional to increased basicity. This was explained by the increasing fraction of un-ionized D molecules at increasing basicity of the culture medium. It is only these electrically neutral D molecules which can penetrate the lipoidal cell membrane to induce formation of CCV. Intracellular presence of D was demonstrated by mass spectrometry methods. The results indicate that D is incorporated intracellularly, that D and not its metabolite(s) is in cells, and suggest that CCV are a result of drug sequesteration.
在培养的大鼠膀胱癌细胞中，二丁酰胺（D）的细胞摄取以及D诱导的透明细胞质空泡（CCV）形成取决于培养基的pH值。在pH 6.0 - 6.7时，药物摄取缓慢，24小时内未形成CCV。在pH 7.0 - 8.0时，D的摄取速率和CCV的早期出现与碱性增加成正比。这可以通过在培养基碱性增加时未电离的D分子比例增加来解释。只有这些电中性的D分子才能穿透脂质细胞膜以诱导CCV的形成。通过质谱方法证实了细胞内存在D。结果表明D被细胞内摄取，细胞内存在的是D而非其代谢产物，并提示CCV是药物隔离的结果。
