Engelholm S A, Spang-Thomsen M, Vindeløv L L, Brünner N
Exp Cell Biol. 1986;54(3):138-48. doi: 10.1159/000163451.
Four human small cell carcinomas of the lung grown in nude mice were exposed to melphalan. Two of the tumors were derived from subpopulations isolated by in vitro cloning from the same tumor biopsy. The chemosensitivity of the tumors was determined by calculating the specific growth delay. Drug-induced changes in the cell cycle were detected by flow cytometric DNA analysis. The specific growth delay of the tumors was very different with the greatest differences between the two subpopulations originating from the same tumor. Melphalan induced a dose-related S phase accumulation in three sensitive tumors, whereas no changes were seen in a resistant tumor. Furthermore, the amount of S phase accumulation reflected the sensitivity to melphalan. The results suggest that heterogeneity in chemosensitivity is an important reason for chemotherapy failures.
将四只在裸鼠体内生长的人肺小细胞癌暴露于美法仑。其中两个肿瘤源自通过体外克隆从同一肿瘤活检样本中分离出的亚群。通过计算特定生长延迟来确定肿瘤的化学敏感性。通过流式细胞术DNA分析检测药物诱导的细胞周期变化。肿瘤的特定生长延迟差异很大，同一肿瘤来源的两个亚群之间差异最大。美法仑在三个敏感肿瘤中诱导了与剂量相关的S期积累，而在一个耐药肿瘤中未观察到变化。此外，S期积累的量反映了对美法仑的敏感性。结果表明，化学敏感性的异质性是化疗失败的一个重要原因。
