Hill B T, Deuchars K, Hosking L K, Ling V, Whelan R D
Cellular Chemotherapy Laboratory, Imperial Cancer Research Fund, London, England.
J Natl Cancer Inst. 1990 Apr 4;82(7):607-12. doi: 10.1093/jnci/82.7.607.
We observed that in vitro exposure of mammalian tumor cells to fractionated x irradiation results in the expression of drug resistance. The cause of this resistance was investigated in a series of Chinese hamster ovary cell lines that had survived exposure to multiple lethal doses of radiation. These cell lines had increased levels of P-glycoprotein (Pgp), the multidrug-resistance-associated membrane glycoprotein. Consistent with the classic multidrug resistance phenotype, they exhibited cross-resistance to multiple drugs, as well as sensitivity to reversal of vincristine resistance by verapamil. However, the cell lines showed no change in their sensitivity to x rays. Pgp overexpression occurred in these cells, despite a lack of Pgp gene amplification or of significant alteration in Pgp messenger RNA levels. Although the cause of increased Pgp levels is not yet known, these data suggest a biological basis for the clinical problem of drug resistance that can occur in previously irradiated tumors.
我们观察到，哺乳动物肿瘤细胞在体外接受分次X射线照射后会产生耐药性。我们在一系列经多次致死剂量辐射后存活下来的中国仓鼠卵巢细胞系中研究了这种耐药性的原因。这些细胞系中P - 糖蛋白（Pgp）水平升高，P - 糖蛋白是一种与多药耐药相关的膜糖蛋白。与经典的多药耐药表型一致，它们对多种药物表现出交叉耐药性，并且对维拉帕米逆转长春新碱耐药性敏感。然而，这些细胞系对X射线的敏感性没有变化。尽管Pgp基因没有扩增，Pgp信使RNA水平也没有显著改变，但这些细胞中仍出现了Pgp过表达。虽然Pgp水平升高的原因尚不清楚，但这些数据为先前接受过照射的肿瘤中可能出现的耐药性临床问题提供了生物学基础。
